進階搜尋


   電子論文尚未授權公開,紙本請查館藏目錄
(※如查詢不到或館藏狀況顯示「閉架不公開」,表示該本論文不在書庫,無法取用。)
系統識別號 U0026-2610201519235700
論文名稱(中文) 探討並建立致癌鋅手指轉錄分子ZNF322A的轉錄調控機制及轉錄調控網路
論文名稱(英文) Characterization of transcriptional mechanism and transcriptional network of oncogenic zinc finger protein ZNF322A
校院名稱 成功大學
系所名稱(中) 基礎醫學研究所
系所名稱(英) Institute of Basic Medical Sciences
學年度 104
學期 1
出版年 104
研究生(中文) 任婕羽
研究生(英文) Jayu Jen
學號 S58981387
學位類別 博士
語文別 英文
論文頁數 123頁
口試委員 指導教授-王憶卿
召集委員-王育民
口試委員-洪建中
口試委員-蔣輯武
口試委員-阮雪芬
口試委員-徐駿森
中文關鍵字 肺癌  ZNF322A  c-Jun  轉錄調控因子  染色體免疫沈澱定序分析  核醣核酸定序分析  蛋白質體學  轉錄調控網路 
英文關鍵字 lung cancer  ZNF322A  c-Jun  transcription factor  ChIP-seq  RNA-seq  proteomics  transcription network 
學科別分類
中文摘要 背景介紹及研究目的:肺癌不論在西方國家或是亞洲國家都占男性及女性癌症致死因素的首位;雖然已有許多研究致力於探討肺癌的致癌機轉,但目前成效仍有限。因此,研究肺癌癌症生成的機制及藉此尋找新穎的治療標的是相當迫切的工作。本實驗在先前的研究中,利用比較基因體學(array-comparative genomic hybridization)的方式,檢驗了四十位亞洲肺癌病人及二十位西方肺癌病人中基因體擴增(Chromosome amplification)及剔除(Chromosome deletion)的狀況,希望可以透過全基因體的檢驗找出肺癌中新穎的致癌基因或抑癌基因。藉此研究我們發現了座落在染色體chromosome 6p22.1的ZNF322A基因,不論是在亞洲或西方肺癌病人中都有顯著基因體擴增的現象。然而,截至目前為止,ZNF322A基因是否過度表現及對肺癌生成的影響機制尚未釐清。
研究結果:在本研究中,我們證實亞洲(79%, 97/123) 及西方肺癌病人(73%, 54/74) 皆有高比例的ZNF322A蛋白質過度表達的現象。多變項Cox迴歸分析顯示ZNF322A可視為肺癌病人的死亡危險指標,同時Kaplan-Meier存活分析也證實ZNF322A蛋白質過度表達的病人有較差的預後(Prognosis)。在肺癌細胞甚至是人類支氣管上皮細胞BEAS-2B中,過度表現ZNF322A會促進細胞的增生(Proliferation)及軟膠細胞群落形成(Soft agar growth)的能力。除此之外,ZNF322A的過量表現也會促進肺癌細胞的爬行(Migration)及侵略(Invasion)能力。相反地,細胞及動物實驗也都證實,抑制ZNF322A的表現能降低肺癌細胞增生、爬行及侵略的能力。為了探討ZNF322A在肺癌中的轉錄調控機制,我們透過體外蛋白與去氧核醣核酸結合試驗(CASTing assay)及染色體免疫沈澱高通量定序(Chromatin-immunoprecipitation-sequencing)首先確認了ZNF322A的去氧核醣核酸結合序列。進一步,藉由整合染色體免疫沈澱高通量定序、全基因體核醣核酸定序(RNA-sequencing)及蛋白質體學(Proteomics),我們發現了許多ZNF322A的轉錄目標基因,其中許多基因已被報導參與在癌症生成的相關過程中,譬如轉錄調控、細胞週期調控及細胞爬行等。在機制上,我們發現ZNF322A和c-Jun會形成複合物,共同結合至下游基因啟動子(Promoter)的AP-1區域,並透過與不同的染色質修飾酵素(Chromatin modifier)結合而影響下游染色質的結構鬆緊,進一步活化了致癌基因類的下游基因,如alpha-adducin及cyclin D1,卻抑制了抑癌基因類的下游基因,如p53。
研究結論:我們的研究結果顯示ZNF322A過度表達會在轉錄層面影響許多下游基因的表現,進一步影響細胞的生長及爬行能力,最終導致肺癌生成及病人不好的預後。我們也透過全基因體分析發現了ZNF322A的去氧核醣核酸結合序列及下游轉錄目標基因。除此之外,基因功能分類分析(Gene Ontology analysis)也顯示,除了細胞生長及爬行能力外,ZNF322A在肺癌幹細胞中似乎也扮演重要角色。未來,我們也將致力釐清ZNF322A在肺癌生成或是肺癌幹細胞中的轉錄調控機制,以期最終能夠建構ZNF322A的轉錄調控網路(transcriptional network)。
英文摘要 Background: Lung cancer is the leading cause of cancer death both in female and in male worldwide. Overall survival of lung cancer patients is still poor, although lots of efforts have done trying to cure lung cancer. Therefore, elucidation of the cellular mechanisms in lung tumorigenesis is important to develop early diagnostic and new effective therapeutic targets. In our previous studies, we examined 18 human genomic imbalance hotspots in 40 Asian and 20 Caucasian lung cancer patients using array comparative genomic hybridization. A putative oncogene ZNF322A, which located at chromosome 6p22.1, was found significantly amplified in both Asian and Caucasian lung cancer patients. However, the oncogenic role of ZNF322A overexpression and its underlying mechanism in lung tumorigenesis remain elusive.
Results: Here, we show high frequency of ZNF322A protein overexpression in Asian (79%, 97/123) and Caucasian (73%, 54/74) lung cancer patients. Multivariate Cox regression analysis indicated that ZNF322A was an independent risk factor for lung cancer poor outcome, corroborating the Kaplan-Meier results that patients with ZNF322A protein overexpression had significantly poorer overall survival than other patients. Overexpression of ZNF322A promoted cell proliferation and soft agar growth by prolonged cell cycle in S phase in multiple lung cell lines, including the immortalized lung cell BEAS-2B. In addition, ZNF322A overexpression enhanced cell migration and invasion. In contrast, knockdown of ZNF322A diminished cell growth, invasion and metastasis abilities in vitro and in vivo. To characterize the transcriptional mechanism of ZNF322A in lung cancer, we first revealed consensus DNA binding motifs of ZNF322A using CASTing (Cyclic amplification and selection of targets) assay and chromatin-immunoprecipitation-sequencing (ChIP-seq) analysis. We then identified putative transcriptional targets of ZNF322A by integrating ChIP-seq, RNA-seq and proteomic datasets. Many of the ZNF322A transcriptional target genes were involved in cancer-related processes, such as transcription, cell cycle regulation and migration. Mechanistically, we found that ZNF322A formed complex with c-Jun and cooperatively activated alpha-adducin and cyclin D1 but repressed p53 gene transcription by recruiting differential chromatin modifiers, such as histone deacetylase 3, in an AP-1 element dependent manner using luciferase promoter activity assay combined with site-directed mutagenesis and sequential ChIP-PCR assay.
Conclusion: Our results provide compelling evidences that overexpression of ZNF322A transcriptionally dysregulates genes in cell growth and motility therefore contributes to lung tumorigenesis and poor prognosis. The unbiased genomic analyses reveal de novo ZNF322A motifs and downstream target genes in lung cancer. Gene ontology analyses of genomic datasets unravel the previously unidentified role of ZNF322A in lung cancer stem cell. Further study will be pursued to elucidate ZNF322A transcriptional mechanism and characterize ZNF322A transcriptional network in lung cancer or lung cancer stem cells.
論文目次 中文摘要 I
ABSTRACT III
誌謝 V
INTRODUCTION 1
I. Clinical significance of lung cancer
1. Clinical significance of lung cancer 1
2. Genetic alterations in lung cancer 1
II. Identify DNA imbalance regions and cancer-related genes in lung cancer
1. Genomic structural alteration in tumorigenesis 2
2. Molecular method to detect genomic structural alteration 3
III. Cys2His2 (C2H2) zinc finger protein
1. General introduction of C2H2 zinc fingers 3
2. Role of ZNF protein in cellular processes 4
3. Previous study of ZNF322A 5
IV. Transcription regulation of downstream genes through AP-1 element
1. AP-1 transcription factor family 6
2. Differential role of c-Jun in tumorigenesis 7
V. Downstream genes of ZNF322A identified in current study
1. Cyclin D1 8
2. p53…….. 9
3. Alpha-adducin 10
4. c-MYC……. 11
STUDY BASIS AND DESIGN 13
MATERIALS AND METHODS 17
1. Study population 17
2. qRT-PCR assay 17
3. Immunohistochemistry assay 17
4. Cell lines and culture conditions 17
5. Immunoblotting analysis 18
6. Plasmid, RNAi and transfection 18
7. Cell proliferation assay 18
8. Anchorage-independent growth assay 18
9. Flow cytometry 19
10. Transwell migration and invasion assay 19
11. Tumor growth assay in vivo 19
12. Experimental metastasis assay in vivo 20
13. Chromatin-immunoprecipitation (ChIP) followed by deep sequencing 20
14. Cyclic amplification and selection of targets assay 21
15. De novo motif discovery and database matching of discovered motifs 21
16. Genome-wide RNA sequencing 22
17. Gene set enrichment analysis 23
18. ChIP-qPCR assay 23
19. Proteomics analysis and Gene Ontology analysis 23
20. Site-directed mutagenesis 26
21. Dual luciferase promoter assay 26
22. Immunoprecipitation assay 26
23. Mutation analysis of p53 gene 27
24. Tumor sphere formation assay 27
25. Statistical analysis 27
RESULTS 29
1. ZNF322A overexpression correlates with poor prognosis in both Asian and Caucasian lung cancer patients 29
2. ZNF322A overexpression promotes cell proliferation and motility in lung cancer cells 30
3. ZNF322A overexpression accelerates tumor growth and tumor metastasis in vivo 31
4. Genome-wide mapping of ZNF322A binding sites in lung cancer cells 32
5. Identify ZNF322A transcriptional targets by integrating ChIP-seq and RNA-seq analyses 33
6. Quantitative proteomics identifies ZNF322A-regulated proteins 35
7. ZNF322A positively regulates ADD1 and CCND1 expression but negatively regulates p53 expression at transcription level 35
8. ZNF322A and c-Jun cooperatively bind to AP-1 elements on the ADD1, CCND1 and p53 promoters 36
9. ZNF322A modulates chromatin structure of ADD1, CCND1 and p53 promoters by recruiting differential chromatin modifiers 37
10. ZNF322A exerts its oncogenic effects in lung cancer via regulation of ADD1, CCND1 and p53 37
DISCUSSION 39
1. ZNF322A amplification in both Asian and Caucasian lung cancer patients 39
2. ZNF322A is a novel transcription factor 40
3. Selective and differential regulation of ZNF322A on downstream gene transcription 40
4. Novel transcription regulation mediated by ZNF322A on ADD1, CCND1 and p53 expression 42
5. A potential role of ZNF322A in pluripotency maintenance in lung cancer context 44
6. ZNF322A negatively regulates c-MYC expression at transcription level 45
REFERENCES 49
TABLES 72
FIGURES 75
APPENDIX TABLES 103
APPENDIX FIGURES 119
PUBLICATION 123
參考文獻 Ahrendt SA, Decker PA, Alawi EA, Zhu Yr YR, Sanchez-Cespedes M, Yang SC, Haasler GB, Kajdacsy-Balla A, Demeure MJ, Sidransky D. Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung. Cancer 2001; 92: 1525-1530.
Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ, Jonat C, Herrlich P, Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell 1987; 49: 729-739.
Bailey TL, Elkan C. Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc Int Conf Intell Syst Mol Biol 1994; 2: 28-36.
Bakiri L, Lallemand D, Bossy-Wetzel E, Yaniv M. Cell cycle-dependent variations in c-Jun and JunB phosphorylation: a role in the control of cyclin D1 expression. EMBO J 2000; 19: 2056-2068.
Bartek J, Lukas J. Mammalian G1- and S-phase checkpoints in response to DNA damage. Curr Opin Cell Biol 2001; 13: 738-747.
Bennett V, Gardner K, Steiner JP. Brain adducin: a protein kinase C substrate that may mediate site-directed assembly at the spectrin-actin junction. J Biol Chem 1988; 263: 5860-5869.
Benos PV, Lapedes AS, Stormo GD. Probabilistic code for DNA recognition by proteins of the EGR family. J Mol Biol 2002; 323: 701-727.
Bhoumik A, Fichtman B, Derossi C, Breitwieser W, Kluger HM, Davis S, Subtil A, Meltzer P, Krajewski S, Jones N, Ronai Z. Suppressor role of activating transcription factor 2 (ATF2) in skin cancer. Proc Natl Acad Sci USA 2008; 105: 1674-1679.
Bianchi F, Nicassio F, Di Fiore PP. Unbiased vs biased approaches to the identification of cancer signature: the case of lung cancer. Cell Cycle 2008; 7: 729-734.
Blackwood EM, Eisenman RN. Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding protein that forms a sequence-specific DNA-binding complex with Myc. Science 1991; 251: 1211-1217.
Blackwood EM, Kretzner L, Eisenman RN. Myc and Max function as a nucleoprotein complex. Curr Opin Genet Dev 1992; 2: 227-235.
Blagosklonny MV. Loss of function and p53 protein stabilization. Oncogene 1997; 15: 1889-1893.
Blobel GA, Nakajima T, Eckner R, Montminy M, Orkin SH. CREB-binding protein cooperates with transcription factor GATA-1 and is required for erythroid differentiation. Proc Natl Acad Sci USA 1998; 95: 2061-2066.
Bouchard C, Thieke K, Maier A, Saffrich R, Hanley-Hyde J, Ansorge W, Reed S, Sicinski P, Bartek J, Eilers M. Direct induction of cyclin D2 by Myc contributes to cell cycle progression and sequestration of p27. EMBO J 1999; 18: 5321-5333.
Boxer RB, Jang JW, Sintasath L, Chodosh LA. Lack of sustained regression of c-MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation. Cancer Cell 2004; 6: 577-586.
Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 2005; 122: 947-956.
Brayer KJ, Kulshreshtha S, Segal DJ. The protein-binding potential of C2H2 zinc finger domains. Cell Biochem Biophys 2008; 51: 9-19.
Casimiro MC, Crosariol M, Loro E, Ertel A, Yu Z, Dampier W, Saria EA, Papanikolaou A, Stanek TJ, Li Z, Wang C, Fortina P, Addya S, Tozeren A, Knudsen ES, Arnold A, Pestell RG. ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice. J Clin Invest 2012; 122: 833-843.
Chang L, Karin M. Mammalian MAP kinase signalling cascades. Nature 2001; 410: 37-40.
Chauhan S, Goodwin JG, Chauhan S, Manyam G, Wang J, Kamat AM, Boyd DD. ZKSCAN3 is a master transcriptional repressor of autophagy. Mol Cell 2013; 50: 16-28.
Chen KY, Chang CH, Yu CJ, Kuo SH, Yang PC. Distribution according to histologic type and outcome by gender and age group in Taiwanese patients with lung carcinoma. Cancer 2005; 103: 2566-2574.
Chen X, Jorgenson E, Cheung ST. New tools for functional genomic analysis. Drug Discov Today 2009; 14: 754-760.
Cheng Y, Liang P, Geng H, Wang Z, Li L, Cheng SH, Ying J, Su X, Ng KM, Ng MH, Mok TS, Chan AT, Tao Q. A novel 19q13 nucleolar zinc finger protein suppresses tumor cell growth through inhibiting ribosome biogenesis and inducing apoptosis but is frequently silenced in multiple carcinomas. Mol Cancer Res 2012; 10: 925-936.
Chinenov Y, Kerppola TK. Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity. Oncogene 2001; 20: 2438-2452.
Chiu R, Angel P, Karin M. Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun. Cell 1989; 59: 979-986.
Coller HA, Grandori C, Tamayo P, Colbert T, Lander ES, Eisenman RN, Golub TR. Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion. Proc Natl Acad Sci USA 2000; 97: 3260-3265.
Cowger JJ, Zhao Q, Isovic M, Torchia J. Biochemical characterization of the zinc-finger protein 217 transcriptional repressor complex: identification of a ZNF217 consensus recognition sequence. Oncogene 2007; 26: 3378-3386.
D’Cruz CM, Gunther EJ, Boxer RB, Hartman JL, Sintasath L, Moody SE, Cox JD, Ha SI, Belka GK, Golant A, Cardiff RD, Chodosh LA. c-MYC induces mammary tumorigenesis by means of a preferred pathway involving spontaneous Kras2 mutations. Nat Med 2001; 7: 235-239.
Dahlman-Wright K, Qiao Y, Jonsson P, Gustafsson JA, Williams C, Zhao C. Interplay between AP-1 and estrogen receptor  in regulating gene expression and proliferation networks in breast cancer cells. Carcinogenesis 2012; 33: 1684-1691.
Dalla-Favera R, Bregni M, Erikson J, Patterson D, Gallo RC, Croce CM. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci USA 1982; 79: 7824-7827.
Dang CV. c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol 1999; 19: 1-11.
Davies JJ, Wilson IM, Lam WL. Array CGH technologies and their applications to cancer genomes. Chromosome Res 2005; 13: 237-248.
Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell 2000; 103: 239-252.
Deng T, Karin M. JunB differs from c-Jun in its DNA-binding and dimerization domains, and represses c-Jun by formation of inactive heterodimers. Genes Dev 1993; 7: 479-490.
Devesa SS, Bray F, Vizcaino AP, Parkin DM. International lung cancer trends by histologic type: male:female differences diminishing and adenocarcinoma rates rising. Int J Cancer 2005; 117: 294-299.
Dinu I, Potter JD, Mueller T, Liu Q, Adewale AJ, Jhangri GS, Einecke G, Famulski KS, Halloran P, Yasui Y. Improving gene set analysis of microarray data by SAM-GS. BMC Bioinformatics 2007; 8: 242.
Donaldson NS, Pierre CC, Anstey MI, Robinson SC, Weerawardane SM, Daniel JM. Kaiso represses the cell cycle gene cyclin D1 via sequence-specific and methyl-CpG-dependent mechanisms. PLoS One 2012; 7: e50398.
Dreszer TR, Karolchik D, Zweig AS, Hinrichs AS, Raney BJ, Kuhn RM, Meyer LR, Wong M, Sloan CA, Rosenbloom KR, Roe G, Rhead B, Pohl A, Malladi VS, Li CH, Learned K, Kirkup V, Hsu F, Harte RA, Guruvadoo L, Goldman M, Giardine BM, Fujita PA, Diekhans M, Cline MS, Clawson H, Barber GP, Haussler D, James Kent W. The UCSC Genome Browser database: extensions and updates 2011. Nucleic Acids Res 2012; 40: D918-923.
Dumortier A, Kirstetter P, Kastner P, Chen S. Ikaros regulates neutrophil differentiation. Blood 2003; 101: 2219-2226.
Eferl R, Wagner EF. AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer 2003; 3: 859-868.
Eisbacher M, Holmes ML, Newton A, Hogg PJ, Khachigian LM, Crossley M, Chong BH. Protein-protein interaction between Fli-1 and GATA-1 mediates synergistic expression of megakaryocyte-specific genes through cooperative DNA binding. Mol Cell Biol 2003; 23: 3427-3441.
Esser C, Scheffner M, Hohfeld J. The chaperone-associated ubiquitin ligase CHIP is able to target p53 for proteasomal degradation. J Biol Chem 2005; 280: 27443-27448.
Evans PM, Liu C. Roles of Krüpel-like factor 4 in normal homeostasis, cancer and stem cells. Acta Biochim Biophys Sin 2008; 40: 554-564.
Fan B, Dachrut S, Coral H, Yuen ST, Chu KM, Law S, Zhang L, Ji J, Leung SY, Chen X. Integration of DNA copy number alterations and transcriptional expression analysis in human gastric cancer. PLoS One 2012; 7: e29824.
Fantl V, Stamp G, Andrews A, Rosewell I, Dickson C. Mice lacking cyclin D1 are small and show defects in eye and mammary gland development. Genes Dev 1995; 9: 2364-2372.
Fernandez PC, Frank SR, Wang L, Schroeder M, Liu S, Greene J, Cocito A, Amati B. Genomic targets of the human c-Myc protein. Genes Dev 2003; 17: 1115-1129.
Fialka I, Schwarz H, Reichmann E, Oft M, Busslinger M, Beug H. The estrogen-dependent c-JunER protein causes a reversible loss of mammary epithelial cell polarity involving a destabilization of adherens junctions. J Cell Biol 1996; 132: 1115-1132.
Font J, Mackay JP. Beyond DNA: zinc finger domains as RNA-binding modules. Methods Mol Biol 2010; 649: 479-491.
Freed-Pastor WA, Prives C. Mutant p53: one name, many proteins. Genes Dev 2012; 26: 1268-1286.
Frietze S, O’Geen H, Blahnik KR, Jin VX, Farnham PJ. ZNF274 recruits the histone methyltransferase SETDB1 to the 3’ ends of ZNF genes. PLoS One 2010; 5: e15082.
Frye M, Gardner C, Li ER, Arnold I, Watt FM. Evidence that Myc activation depletes the epidermal stem cell compartment by modulating adhesive interactions with the local microenvironment. Development 2003; 130: 2793-2808.
Fu M, Wang C, Li Z, Sakamaki T, Pestell RG. Minireview: Cyclin D1: normal and abnormal functions. Endocrinology 2004; 145: 5439-5447.
Fukata Y, Oshiro N, Kinoshita N, Kawano Y, Matsuoka Y, Bennett V, Matsuura Y, Kaibuchi K. Phosphorylation of adducin by Rho-kinase plays a crucial role in cell motility. J Cell Biol 1999; 145: 347-361.
Gardner K, Bennett V. Modulation of spectrin-actin assembly by erythrocyte adducin. Nature 1987; 328: 359-362.
Garg V, Kathiriya IS, Barnes R, Schluterman MK, King IN, Butler CA, Rothrock CR, Eapen RS, Hirayama-Yamada K, Joo K, Matsuoka R, Cohen JC, Srivastava D. GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature 2003; 424: 443-447.
Gocke CB, Yu H. ZNF198 stabilizes the LSD1-CoREST-HDAC1 complex on chromatin through its MYM-type zinc fingers. PLoS One 2008; 3: e3255.
Golomb L, Volarevic S, Oren M. p53 and ribosome biogenesis stress: the essentials. FEBS Lett 2014; 588: 2571-2579.
Grandori C, Cowley SM, James LP, Eisenman RN. The Myc/Max/Mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol 2000; 16: 653-699.
Gregory RC, Taxman DJ, Seshasayee D, Kensinger MH, Bieker JJ, Wojchowski DM. Functional interaction of GATA1 with erythroid Krüppel-like factor and Sp1 at defined erythroid promoters. Blood 1996; 87: 1793-1801.
Guo QM, Malek RL, Kim S, Chiao C, He M, Ruffy M, Sanka K, Lee NH, Dang CV, Liu ET. Identification of c-myc responsive genes using rat cDNA microarray. Cancer Res 2000; 60: 5922-5928.
Gupta S, Stamatoyannopoulos JA, Bailey TL, Noble WS. Quantifying similarity between motifs. Genome Biol 2007; 8: R24.
Halazonetis TD, Georgopoulos K, Greenberg ME, Leder P. c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. Cell 1988; 55: 917-924.
Herbst RS, Heymach JV, Lippman SM. Lung cancer. N Engl J Med 2008; 359: 1367-1380.
Hermeking H, Rago C, Schuhmacher M, Li Q, Barrett JF, Obaya AJ, O’Connell BC, Mateyak MK, Tam W, Kohlhuber F, Dang CV, Sedivy JM, Eick D, Vogelstein B, Kinzier KW. Identification of CDK4 as a target of c-MYC. Proc Natl Acad Sci USA 2000; 97: 2229-2234.
Herold S, Wanzel M, Beuger V, Frohme C, Beul D, Hillukkala T, Syvaoja J, Saluz HP, Haenel F, Eilers M. Negative regulation of the mammalian UV response by Myc through association with Miz-1. Mol Cell 2002; 10: 509-521.
Hou J, Aerts J, den Hamer B, van Ijcken W, den Bakker M, Riegman P, van der Leest C, van der Spek P, Foekens JA, Hoogsteden HC, Grosveld F, Philipsen S. Gene expression-based classification of non-small cell lung carcinomas and survival prediction. PLoS One 2010; 5: e10312.
Hu R, Peng G, Dai H, Breuer EK, Stemke-Hale K, Li K, Gonzalez-Angulo AM, Mills GB, Lin SY. ZNF668 functions as a tumor suppressor by regulating p53 stability and function in breast cancer. Cancer Res 2011; 71: 6524-6534.
Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4: 44-57.
Hughes CA, Bennett V. Adducin: a physical model with implications for function in assembly of spectrin-actin complexes. J Biol Chem 1995; 270: 18990-18996.
Ivanov VN, Bhoumik A, Krasilnikov M, Raz R, Owen-Schaub LB, Levy D, Horvath CM, Ronai Z. Cooperation between STAT3 and c-jun suppresses Fas transcription. Mol Cell 2001; 7: 517-528.
Iwakoshi NN, Lee AH, Vallabhajosyula P, Otipoby KL, Rajewsky K, Glimcher LH. Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1. Nat Immunol 2003; 4: 321-329.
Jänne PA, Engelman JA, Johnson BE. Epidermal growth factor receptor mutations in non-small-cell lung cancer: implications for treatment and tumor biology. J Clin Oncol 2005; 23: 3227-3234.
Jeon BN, Kim MK, Yoon JH, Kim MY, An H, Noh HJ, Choi WI, Koh DI, Hur MW. Two ZNF509 (ZBTB49) isoforms induce cell-cycle arrest by activating transcription of p21/CDKN1A and RB upon exposure to genotoxic stress. Nucleic Acids Res 2014; 42: 11447-11461.
Jheon AH, Ganss B, Cheifetz S, Sodek J. Characterization of a novel KRAB/C2H2 zinc finger transcription factor involved in bone development. J Biol Chem 2001; 276: 18282-18289.
Jochum W, Passegué E, Wagner EF. AP-1 in mouse development and tumorigenesis. Oncogene 2001; 20: 2401-2412.
Jones S. An overview of the basic helix-loop-helix proteins. Genome Biol 2004; 5: 226.
Joshi R, Gilligan DM, Otto E, McLaughlin T, Bennett V. Primary structure and domain organization of human alpha and beta adducin. J Cell Biol 1991; 115: 665-675.
Kallioniemi A. CGH microarrays and cancer. Curr Opin Biotechnol 2008; 19: 36-40.
Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MD, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley TJ, Wilson RK, Raphael BJ, Ding L. Mutational landscape and significance across 12 major cancer types. Nature 2013; 502: 333-339.
Kang JU, Koo SH, Kwon KC, Park JW. Frequent silence of chromosome 9p, homozygous DOCK8, DMRT1 and DMRT3 deletion at 9p24.3 in squamous cell carcinoma of the lung. Int J Oncol 2010; 37: 327-335.
Kim G, Khanal P, Lim SC, Yun HJ, Ahn SG, Ki SH, Choi HS. Interleukin-17 induces AP-1 activity and cellular transformation via upregulation of tumor progression locus 2 activity. Carcinogenesis 2013; 34: 341-350.
Kim MK, Shin JM, Eun HC, Chung JH. The role of p300 histone acetyltransferase in UV-induced histone modifications and MMP-1 gene transcription. PLoS One 2009; 4: e4864.
Klug A, Schwabe JW. Protein motifs 5. Zinc fingers. FASEB J 1995; 9: 597-604.
Kouzarides T, Ziff E. The role of the leucine zipper in the fos-jun interaction. Nature 1988; 336: 646-651.
Kushibiki T, Tu Y, Abu-Yousif AO, Hasan T. Photodynamic activation as a molecular switch to promote osteoblast cell differentiation via AP-1 activation. Sci Rep 2015; 5: 13114.
Kuttler F, Mai S. c-Myc, genomic instability and disease. Genome Dyn 2006; 1: 171-190.
Lai KP, Chen J, He M, Ching AK, Lau C, Lai PB, To KF, Wong N. Overexpression of ZFX confers self-renewal and chemoresistance properties in hepatocellular carcinoma. Int J Cancer 2014; 135: 1790-1799.
Laity JH, Dyson HJ, Wright PE. DNA-induced alpha-helix capping in conserved linker sequences is a determinant of binding affinity in Cys(2)-His(2) zinc fingers. J Mol Biol 2000; 295: 719-727.
Lamb J, Ramaswamy S, Ford HL, Contreras B, Martinez RV, Kittrell FS, Zahnow CA, Patterson N, Golub TR, Ewen ME. A mechanism of cyclin D1 action encoded in the patterns of gene expression in human cancer. Cell 2003; 114: 323-334.
Lamb RF, Hennigan RF, Turnbull K, Katsanakis KD, MacKenzie ED, Birnie GD, Ozanne BW. AP-1-mediated invasion requires increased expression of the hyaluronan receptor CD44. Mol Cell Biol 1997; 17: 963-976.
Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann N, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blöcker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowski J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ; International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 2001; 409: 860-921.
Lang GA, Iwakuma T, Suh YA, Liu G, Rao VA, Parant JM, Valentin-Vega YA, Terzian T, Caldwell LC, Strong LC, El-Naggar AK, Lozano G. Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell 2004; 119: 861-872.
Li D, Marchenko ND, Schulz R, Fischer V, Velasco-Hernandez T, Talos F, Moll UM. Functional inactivation of endogenous MDM2 and CHIP by HSP90 causes aberrant stabilization of mutant p53 in human cancer cells. Mol Cancer Res 2011; 9: 577-588.
Li X, Matsuoka Y, Bennett V. Adducin preferentially recruits spectrin to the fast growing ends of actin filaments in a complex requiring the MARCKS-related domain and a newly defined oligomerization domain. J Biol Chem 1998; 273: 19329-19338.
Li Y, Wang Y, Zhang C, Yuan W, Wang J, Zhu C, Chen L, Huang W, Zeng W, Wu X, Liu M. ZNF322, a novel human C2H2 Kruppel-like zinc-finger protein, regulates transcriptional activation in MAPK signaling pathways. Biochem Biophys Res Commun 2004; 325: 1383-1392.
Lin WT, Hung WN, Yian YH, Wu KP, Han CL, Chen YR, Chen YJ, Sung TY, Hsu WL. Multi-Q: a fully automated tool for multiplexed protein quantitation. J Proteome Res 2006; 5: 2328-2338.
Lin X, Huo Z, Liu X, Zhang Y, Li L, Zhao H, Yan B, Liu Y, Yang Y, Chen YH. A novel GATA6 mutation in patients with tetralogy of Fallot or atrial septal defect. J Hum Genet 2010; 55: 662-667.
Liu H, Radisky DC, Yang D, Xu R, Radisky ES, Bissell MJ, Bishop JM. MYC suppresses cancer metastasis by direct transcriptional silencing of v and 3 integrin subunits. Nat Cell Biol 2012; 14: 567-574.
Lo FY, Chang JW, Chang IS, Chen YJ, Hsu HS, Huang SF, Tsai FY, Jiang SS, Kanteti R, Nandi S, Salgia R, Wang YC. The database of chromosome imbalance regions and genes resided in lung cancer from Asian and Caucasian identified by array-comparative genomic hybridization. BMC Cancer 2012; 12: 235.
Louro ID, Bailey EC, Li X, South LS, McKie-Bell PR, Yoder BK, Huang CC, Johnson MR, Hill AE, Johnson RL, Ruppert JM. Comparative gene expression profile analysis of GLI and c-MYC in an epithelial model of malignant transformation. Cancer Res 2002; 62: 5867-5873.
Lu D, Chen S, Tan X, Li N, Liu C, Li Z, Liu Z, Stupack DG, Reisfeld RA, Xiang R. Fra-1 promotes breast cancer chemosensitivity by driving cancer stem cells from dormancy. Cancer Res 2012; 72: 3451-3456.
Ma H, Ng HM, Teh X, Li H, Lee YH, Chong YM, Loh YH, Collins JJ, Feng B, Yang H, Wu Q. Zfp322a regulates mouse ES cell pluripotency and enhances reprogramming efficiency. PLoS Genet 2014; 10: e1004038.
Ma J, Zhang L, Han W, Shen T, Ma C, Liu Y, Nie X, Liu M, Ran Y, Zhu D. Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells. J Lipid Res 2012; 53: 1093-1105.
Mahony S, Benos PV. STAMP: a web tool for exploring DNA-binding motif similarities. Nucleic Acids Res 2007; 35: W253-258.
Manunta P, Barlassina C, Bianchi G. Adducin in essential hypertension. FEBS Lett 1998; 430: 41-44.
Matsuoka Y, Li X, Bennett V. Adducin is an in vivo substrate for protein kinase C: phosphorylation in the MARCKS-related domain inhibits activity in promoting spectrin-actin complexes and occurs in many cells, including dendritic spines of neurons. J Cell Biol 1998; 142: 485-497.
Maya R, Balass M, Kim ST, Shkedy D, Leal JF, Shifman O, Moas M, Buschmann T, Ronai Z, Shiloh Y, Kastan MB, Katzir E, Oren M. ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Genes Dev 2001; 15: 1067-1077.
McCarty AS, Kleiger G, Eisenberg D, Smale ST. Selective dimerization of a C2H2 zinc finger subfamily. Mol Cell 2003; 11: 459-470.
Meixner A, Karreth F, Kenner L, Penninger JM, Wagner EF. Jun and JunD-dependent functions in cell proliferation and stress response. Cell Death Differ 2010; 17: 1409-1419.
Merico D, Isserlin R, Stueker O, Emili A, Bader GD. Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS One 2010; 5: e13984.
Meruvu S, Hugendubler L, Mueller E. Regulation of adipocyte differentiation by the zinc finger protein ZNF638. J Biol Chem 2011; 286: 26516-26523.
Ministry of Health and Welfare, R.O.C.T. General Health Statistics. 2014.
Minna JD, Roth JA, Gazdar AF. Focus on lung cancer. Cancer Cell 2002; 1: 49-52.
Mirza A, Wu Q, Wang L, McClanahan T, Bishop WR, Gheyas F, Ding W, Hutchins B, Hockenberry T, Kirschmeier P, Greene JR, Liu S. Global transcriptional program of p53 target genes during the process of apoptosis and cell cycle progression. Oncogene 2003; 22: 3645-3654.
Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B. Mapping and quantifying mammalian transcriptomes by RNA-seq. Nat Methods 2008; 5: 621-628.
Motokura T, Bloom T, Kim HG, Jüppner H, Ruderman JV, Kronenberg HM, Arnold A. A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature 1991; 350: 512-515.
Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 2008; 26: 101-106.
Neiman PE, Ruddell A, Jasoni C, Loring G, Thomas SJ, Brandvold KA, Lee Rm, Burnside J, Delrow J. Analysis of gene expression during myc oncogene-induced lymphomagenesis in the bursa of Fabricius. Proc Natl Acad Sci USA 2001; 98: 6378-6383.
Nesbit CE, Tersak JM, Grove LE, Drzal A, Choi H, Prochownik EV. Genetic dissection of c-myc apoptotic pathways. Oncogene 2000; 19: 3200-3212.
Nesbit CE, Tersak JM, Prochownik EV. MYC oncogenes and human neoplastic disease. Oncogene 1999; 18: 3004-3016.
Ogawa S, Lozach J, Jepsen K, Sawka-Verhelle D, Perissi V, Sasik R, Rose DW, Johnson RS, Rosenfeld MG, Glass CK. A nuclear receptor corepressor transcriptional checkpoint controlling activator protein 1-dependent gene networks required for macrophage activation. Proc Natl Acad Sci USA 2004; 101: 14461-14466.
Okayama H, Kohno T, Ishii Y, Shimada Y, Shiraishi K, Iwakawa R, Furuta K, Tsuta K, Shibata T, Yamamoto S, Watanabe S, Sakamoto H, Kumamoto K, Takenoshita S, Gotoh N, Mizuno H, Sarai A, Kawano S, Yamaguchi R, Miyano S, Yokota J. Identification of genes upregulated in ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinomas. Cancer Res 2012; 72: 100-111.
Olive KP, Tuveson DA, Ruhe ZC, Yin B, Willis NA, Bronson RT, Crowley D, Jacks T. Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell 2004; 119: 847-860.
Oren M, Rotter V. Mutant p53 gain-of-function in cancer. Cold Spring Harb Perspect Biol 2010; 2: a001107.
Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, Mardis E, Kupfer D, Wilson R, Kris M, Varmus H. EGF receptor gene mutations are common in lung cancers from “nerve smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA 2004; 101: 13306-13311.
Passegué E, Wagner EF. JunB suppresses cell proliferation by transcriptional activation of p16INK4a expression. EMBO J 2000; 19: 2969-2979.
Pinkel D, Albertson DG. Array comparative genomic hybridization and its application in cancer. Nat Genet 2005; 37: 11-17.
Prendergast GC, Ziff EB. Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region. Science 1991; 251: 186-189.
Pulverer BJ, Kyriakis JM, Avruch J, Nikolakaki E, Woodgett JR. Phosphorylation of c-jun mediated by MAP kinases. Nature 1991; 353: 670-674.
Reimold AM, Iwakoshi NN, Manis J, Vallabhajosyula P, Szomolanyi-Tsuda E, Gravallese EM, Friend D, Grusby MJ, Alt F, Glimcher LH. Plasma cell differentiation requires the transcription factor XBP-1. Nature 2001; 412: 300-307.
Rekhtman N, Radparvar F, Evans T, Skoultchi AI. Direct interaction of hematopoietic transcription factors PU.1 and GATA-1: functional antagonism in erythroid cells. Genes Dev 1999; 13: 1398-1411.
Riely GJ, Marks J, Pao W. KRAS mutations in non-small cell lung cancer. Proc Am Thorac Soc 2009; 6: 201-205.
Sakamaki T, Casimiro MC, Ju X, Quong AA, Katiyar S, Liu M, Jiao X, Li A, Zhang X, Lu Y, Wang C, Byers S, Nicholson R, Link T, Shemluck M, Yang J, Fricke ST, Novikoff PM, Papanikolaou A, Arnold A, Albanese C, Pestell R. Cyclin D1 determines mitochondrial function in vivo. Mol Cell Biol 2006; 26: 5449-5469.
Sant M, Allemani C, Santaquilani M, Knijn A, Marchesi F, Capocaccia R; EUROCARE Working Group. EUROCARE-4. Survival of cancer patients diagnosed in 1995-1999. Results and commentary. Eur J Cancer 2009; 45: 931-991.
Scannell DR, Wolfe K. Rewiring the transcriptional regulatory circuits of cells. Genome Biol 2004; 5: 206.
Schlagbauer-Wadl H, Griffioen M, van Elsas A, Schrier PI, Pustelnik T, Eichler HG, Wolff K, Pehamberger H, Jansen B. Influence of increased c-Myc expression on the growth characteristics of human melanoma. J Invest Dermatol 1999; 112: 332-336.
Schneider KU, Dietrich D, Fleischhacker M, Leschber G, Merk J, Schäper F, Stapert HR, Vossenaar ER, Weickmann S, Liebenberg V, Kneip C, Seegebarth A, Erdogan F, Rappold G, Schmidt B. Correlation of SHOX2 gene amplification and DNA methylation in lung cancer tumors. BMC cancer 2011; 11: 102.
Schreiber M, Kolbus A, Piu F, Szabowski A, Möhle-Steinlein U, Tian J, Karin M, Angel P, Wagner EF. Control of cell cycle progression by c-Jun is p53 dependent. Genes Dev 1999; 13: 607-619.
Schütte J, Viallet J, Nau M, Segal S, Fedorko J, Minna J. jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun. Cell 1989; 59: 987-997.
Schwab M. Oncogene amplification in solid tumors. Semin Cancer Biol 1999; 9: 319-325.
Scott MP, Tamkun JW, Hartzell GW 3rd. The structure and function of the homeodomain. Biochim Biophys Acta 1989; 989: 25-48.
Sekido Y, Fong KM, Minna JD. Molecular genetics of lung cancer. Annu Rev Med 2003; 54: 73-87.
Selamat SA, Chung BS, Girard L, Zhang W, Zhang Y, Campan M, Siegmund KD, Koss MN, Hagen JA, Lam WL, Lam S, Gazdar AF, Laird-Offringa IA. Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression. Genome Res 2012; 22: 1197-1211.
Shaulian E, Schreiber M, Piu F, Beeche M, Wagner EF, Karin M. The mammalian UV response: c-Jun induction is required for exit from p53-imposed growth arrest. Cell 2000; 103: 897-907.
Sheiness D, Bishop JM. DNA and RNA from uninfected vertebrate cells contain nucleotide sequences related to the putative transforming gene of avian myelocytomatosis virus. J Virol 1979; 31: 514-521.
Shen Q, Uray IP, Li Y, Krisko TI, Strecker TE, Kim HT, Brown PH. The AP-1 transcription factor regulates breast cancer cell growth via cyclins and E2F factors. Oncogene 2008; 27: 366-377.
Sherr CJ. Cancer cell cycles. Science 1996; 274: 1672-1677.
Shi Y, Au JS, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, Heeroma K, Itoh Y, Cornelio G, Yang PC. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol 2014; 9: 154-162.
Shigematsu H, Gazdar AF. Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers. Int J Cancer 2006; 118: 257-262.
Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, Haslam SZ, Bronson RT, Elledge SJ, Weinberg RA. Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell 1995; 82: 621-630.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65: 5-29.
Smeal T, Binetruy B, Mercola DA, Birrer M, Karin M. Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73. Nature 1991; 354: 494-496.
Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 2011; 27: 431-432.
Song H, Hollstein M, Xu Y. p53 gain-of-function cancer mutants induce genetic instability by inactivating ATM. Nat Cell Biol 2007; 9: 573-580.
Soo RA, Loh M, Mok TS, Ou SH, Cho BC, Yeo WL, Tenen DG, Soong R. Ethnic differences in survival outcome in patients with advanced stage non-small cell lung cancer: results of a meta-analysis of randomized controlled trials. J Thorac Oncol 2011; 6: 1030-1038.
Sreeramaneni R, Chaudhry A, McMahon M, Sherr CJ, Inoue K. Ras-Raf-Arf signaling critically depends on the Dmp1 transcription factor. Mol Cell Biol 2005; 25: 220-232.
Staller P, Peukert K, Kiermaier A, Seoane J, Lukas J, Karsunky H, Möröy T, Bartek J, Massagué J, Hänel F, Eilers M. Repression of p15INK4b expression by Myc through association with Miz-1. Nat Cell Biol 2001; 3: 392-399.
Sundgvist A, Zieba A, Vasilaki E, Herrera Hidalgo C, Söderberg O, Koinuma D, Miyazono K, Heldin CH, Landegren U, Ten Dijke P, van Dam H. Specific interactions between Smad proteins and AP-1 components determine TGF-induced breast cancer cell invasion. Oncogene 2013; 32: 3603-3615.
Swamynathan SK, Katz JP, Kaestner KH, Ashery-Padan R, Crawford MA, Piatigorsky J. Conditional deletion of the mouse Klf4 gene results in corneal epithelial fragility, stromal edema, and loss of conjunctival goblet cells. Mol Cell Biol 2007; 27: 182-194.
Taub R, Kirsch I, Morton C, Lenoir G, Swan D, Tronick S, Aaronson S, Leder P. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci USA 1982; 79: 7837-7841.
Tchakarska G, Roussel M, Troussard X, Sola B. Cyclin D1 inhibits mitochondrial activity in B cells. Cancer Res 2011; 71: 1690-1699.
Tian C, Xing G, Xie P, Lu K, Nie J, Wang J, Li L, Gao M, Zhang L, He F. KRAB-type zinc-finger protein Apak specifically regulates p53-dependent apoptosis. Nat Cell Biol 2009; 11: 580-591.
Tupler R, Perini G, Green MR. Expressing the human genome. Nature 2001; 409: 832-833.
Vakifahmetoglu-Norberg H, Kim M, Xia HG, Iwanicki MP, Ofengeim D, Coloff JL, Pan L, Ince TA, Kroemer G, Brugge JS, Yuan J. Chaperone-mediated autophagy degrades mutant p53. Genes Dev 2013; 27: 1718-1730.
Valente LJ, Gray DH, Michalak EM, Pinon-Hofbauer J, Egle A, Scott CL, Janic A, Strasser A. p53 efficiently suppresses tumor development in the complete absence of its cell-cycle inhibitory and proapoptotic effectors p21, Puma, and Noxa. Cell Rep 2013; 3: 1339-1345.
Vizcaino JA, Deutsch EW, Wang R, Csordas A, Reisinger F, Rios D, Dianes JA, Sun Z, Farrah T, Bandeira N, Binz PA, Xenarios I, Eisenacher M, Mayer G, Gatto L, Campos A, Chalkley RJ, Kraus HJ, Albar JP, Martinez-Bartolomé S, Apweiler R, Omenn GS, Martens L, Jones AR, Hermjakob H. ProteomeXchange provides globally coordinated proteomics data submission and dissemination. Nat Biotechnol 2014; 32: 223-226.
Vousden KH, Lane DP. p53 in health and disease. Nat Rev Mol Cell Biol 2007; 8: 275-283.
Wachi S, Yoneda K, Wu R. Interactome-transcriptome analysis reveals the high centrality of genes differentially expressed in lung cancer tissues. Bioinformatics 2005; 21: 4205-4208.
Wagner S, Hess MA, Ormonde-Hanson P, Malandro J, Hu H, Chen M, Kehrer R, Frodsham M, Schumacher C, Beluch M, Honer C, Skolnick M, Ballinger D, Bowen BR. A broad role for the zinc finger protein ZNF202 in human metabolism. J Biol Chem 2000; 275: 15685-15690.
Waikel RL, Kawachi Y, Waikel PA, Wang XJ, Roop DR. Deregulated expression of c-Myc depletes epidermal stem cells. Nat Genet 2001; 28: 165-168.
Wang BS, Grant RA, Pabo CO. Selected peptide extension contacts hydrophobic patch on neighboring zinc finger and mediates dimerization on DNA. Nat Struct Biol 2001; 8: 589-593.
Wang YC, Chen CY, Chen SK, Cherng SH, Ho WL, Lee H. High frequency of deletion mutations in p53 gene from squamous cell lung cancer patients in Taiwan. Cancer Res 1998; 58: 328-333.
Wei Z, Yang Y, Zhang P, Andrianakos R, Hasegawa K, Lyu J, Chen X, Bai G, Liu C, Pera M, Lu W. Klf4 interacts directly with Oct4 and Sox2 to promote reprogramming. Stem Cells 2009; 27: 2969-2978.
Welm AL, Kim S, Welm BE, Bishop JM. MET and MYC cooperate in mammary tumorigenesis. Proc Natl Acad Sci USA 2005; 102: 4324-4329.
Wernig M, Meissner A, Cassady JP, Jaenisch R. c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell 2008; 2: 10-12.
Wierstra I, Alves J. FOXM1c and Sp1 transactivate the P1 and P2 promoters of human c-myc synergistically. Biochem Biophys Res Commun 2007; 352: 61-68.
Wierstra I, Alves J. The c-myc promoter: still MysterY and challenge. Adv Cancer Res 2008; 99: 113-333.
Wittekindt NE, Hörtnagel K, Geltinger C, Polack A. Activation of c-myc promoter P1 by immunoglobulin kappa gene enhancers in Burkitt lymphoma: functional characterization of the intron enhancer motifs kappaB, E box 1 and E box 2, and of the 3' enhancer motif PU. Nucleic Acids Res 2000; 28: 800-808.
Wolfe SA, Nekludova L, Pabo CO. DNA recognition by Cys2His2 zinc finger proteins. Annu Rev Biophys Biomol Struct 2000; 29: 183-212.
Wooster et al., unpublished data deposited in Oncomine database: https://www.oncomine.org/
Wu CC, Hsu HY, Liu HP, Chang JW, Chen YT, Hsieh WY, Hsieh JJ, Hsieh MS, Chen YR, Huang SF. Reversed mutation rates of KRAS and EGFR genes in adenocarcinoma of the lung in Taiwan and their implications. Cancer 2008; 113: 3199-3208.
Wu YH, Hu CW, Chien CW, Chen YJ, Huang HC, Juan HF. Quantitative proteomic analysis of human lung tumor xenografts treated with the ectopic ATP synthase inhibitor citreoviridin. PLoS One 2013; 8: e70642.
Yang G, Ma F, Zhong M, Fang L, Peng Y, Xin X, Zhong J, Yuan F, Gu H, Zhu W, Zhang Y. ZNF703 acts as an oncogene that promotes progression in gastric cancer. Oncol Rep 2014; 31: 1877-1882.
Ye BH, Cattoretti G, Shen Q, Zhang J, Hawe N, de Waard R, Leung C, Nouri-Shirazi M, Orazi A, Chaganti RS, Rothman P, Stall AM, Pandolfi PP, Dalla-Favera R. The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation. Nat Genet 1997; 16: 161-170.
Yoshimi I, Ohshima A, Ajiki W, Tsukuma H, Sobue T. A comparison of trends in the incidence rate of lung cancer by histological type in the Osaka Cancer Registry, Japan and in the Surveillance, Epidemiology and End Results Program, USA. Jpn J Clin Oncol 2003; 33: 98-104.
Yu J, Liang QY, Wang J, Cheng Y, Wang S, Poon TC, Go MY, Tao Q, Chang Z, Sung JJ. Zinc-finger protein 331, a novel putative tumor suppressor, suppresses growth and invasiveness of gastric cancer. Oncogene 2013; 32: 307-317.
Zhang L, Xu Z, Xu X, Zhang B, Wu H, Wang M, Zhang X, Yang T, Cai J, Yan Y, Mao F, Zhu W, Shao Q, Qian H, Xu W. SALL4, a novel marker for human gastric carcinogenesis and metastasis. Oncogene 2014; 33: 5491-5500.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2018-10-29起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw