Oncogenic activation of ERG: A predominant mechanism in prostate cancer

Journal of Carcinogenesis

Volumn 10, Issue , 2011, Pages 10-21

  Sreenath, Taduru ^a   Dobi, Albert ^a   Petrovics, Gyorgy ^a   Srivastava, Shiv ^a  

^a Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center   (United States)

Author keywords

androgen receptor; ERG; oncoprotein; patient stratification; prostate cancer; TMPRSS2 ERG

Indexed keywords

ENTINOSTAT; HISTONE DEACETYLASE INHIBITOR; ORGANOLEAD COMPOUND; TRANSCRIPTION FACTOR ERG; TSA; UNCLASSIFIED DRUG; VORINOSTAT; VPA; YK 4 279;

APOPTOSIS; CANCER CELL; CARCINOGENESIS; GENE ACTIVATION; GENE EXPRESSION; GENE FUNCTION; GENE FUSION; GENE STRUCTURE; GENE TARGETING; GENETIC TRANSCRIPTION; HUMAN; NONHUMAN; PROSTATE CANCER; REVIEW;

EID: 84860128746     PISSN: 09746773     EISSN: 14773163     Source Type: Journal    
DOI: 10.4103/1477-3163.91122     Document Type: Review

References (156)

1. Siegel R. Ward E, Brawley O, Jemal A Cancer statistics, 201 I: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer j Clin 2011:6!:212-36.
2. Williams H, Powell IJ. Epidemiology, pathology, and genetics of prostate cancer among African Americans compared with other ethnicities. Methods Mol Bio! 2009;472:439-53.
3. Zeigier-johnson CM, Rennert H, Mitta! RD, jaiioh M, Sachdeva R Maikowicz SB, et al. Evaluation of prostate cancer characteristics in four populations worldwide. Can j Urol 2008;15:4056-64.
4. Kheirandish P, Chinegwundoh F Ethnic differences in prostate cancer. Br J Cancer 2011 I; 105:481-5.
5. Zeigier-johnson CM, Spnngler E, jnlloh M, Gueye SM, Kennert H, Rebbeck TR Genetic susceptibility to prostate cancer in men of African descent: implications for global disparities in incidence and outcomes. Can J Urol 2008:15:3872-82.
6. LangebERGWJ, Isaacs WB, Stanford JL Genetic etiology of hereditary prostate cancer. Front Biosci 2007; 12:4101-10.
7. Sartor AO, Hricak H, Wheeler TM, Coleman J, Penson DF Carroll PR et al. Evaluating localized prostate cancer and identifying candidates for focal therapy. Urology 2008;72(6 Supp! S) 12-24.
8. De Marzo AM, Hatz EA Sutciiffe S, Xu j, Gronberg H, Drake CG, et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer 2007:7:256-69. (Pubitemid 46486616)
9. Richter E, Srivastava S, Dobi A Androgen receptor and prostate cancer. Prostate Cancer Prostatic Dis 2007; 10:114-8. (Pubitemid 46881662)
10. Yu J. Yu J, Mani RS, Cao Q, Brenner Cj, Cao X. et al. An integrated network of androgen receptor, polycomb, andTMPRSS2-RG gene fusions in prostate cancer progression. Cancer Cell 2010; 17:443-54.
11. Kumar-SinhaCJbmlinsSAChinnaiyanAM. Recurrent gene fusions in prostate cancer. Nat Rev Cancer 2008:8:497-511.
12. Knudsen BS, Vasioukhin V Mechanisms of prostate cancer initiation and progression. Adv Cancer Res 2010;109:1-50.
13. Salinas CA Kwon E, Carlson CS, Koopmeiners JS, Feng Z, Karyadi DM, et al. Multiple independent genetic variants in the 8q24 region are associated with prostate cancer risk. Cancer Epidemiol Biomarkers Prev 2008:17:1203-13.
14. Krai M, RosinskaV Student V, Grepl M, Hrabec M, Bouchal J. Genetic determinants of prostate cancer: a review. Biomed Pap Med Fac UnivPalacky Olomouc Czech Repub 2011; 155:3-9.
15. Witte JS. Prostate cancer genomics: towards a new understanding. Nat Rev Genet 2009:10:77-82.
16. Pomerantz MM, Freedmnn ML Genetics of prostate cancer risk. Mt Sinai j Med 20! 0:77:643-54.
17. Amundadottir LT, Sulem RGudmundssonJ, HelgasonA Baker AAgnarsson BA et al. A common variant associated with prostate cancer in European nndAfrican populations. Nat Genet 2006;38:652-8. (Pubitemid 43927306)
18. R-eedman ML Haiman CA Patterson N. McDonald Gj, landonAWaliszewska A et al. Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men. Proc Natl Acad Sci USA 2006; 103:14068-73. (Pubitemid 44452981)
19. Eeles RA Kote-jarai Z, Giles GG. OlamaAA Guy M, jugurnauth SK. et al. Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet 2008:40:316-21. (Pubitemid 351311772)
20. Thomas G, Jacobs KB. Yeager M, Kraft RWacholder S, Orr N, et al. Multiple loci identified in a genome-wide association study of prostate cancer. Nat Genet 2008:40:310-5. (Pubitemid 351311773)
21. Ghoussnini M, SongH, KoesslerT, A! OlamaAA Kote-jarai Z, Driver KE, et al. Multiple Loci with different cancer specificities within the 8q24 gene desert, j Natl Cancer Inst 2008;100:962-6. (Pubitemid 351957516)
22. Whitman Ej, Pomerantz M. Chen Y, Chamberlin MM, Furusato B, Gao C. et al. Prostate cancer risk allele specific for African descent associates with pathologic stage at prostatectomy. Cancer Epidemiol Biomarkers Prev 2010:19:1-8.
23. Pomerantz MM, ShresthaY, Flavin Rj, Regan MM, Penney KL, Mucci LA et al. Analysis of the lOql I cancer risk locus implicates MSMB and NCOA4 in human prostate tumorigenesis. PLoS Genet 2010;6:e 1001204.
24. Zheng SL Sun J. Wiklund F Smith S, Stattin RLi G, et al. Cumulative association of five genetic variants with prostate cancer. N Engl j Med 2008;358:910-9. (Pubitemid 351397090)
25. Shah S, Small E. Emerging biological observations in prostate cancer. Expert Rev Anticancer Ther 2010; 10:89-101.
26. Berger MF Lawrence MS, Demichelis F DrierY, Cibulskis K, Sivachenko AY et al. The genomic complexity of primary human prostate cancer. Nature 2011;470:214-20.
27. Carver BS. TranJ. GopalanA ChenZ, Shaikh S, Carracedo A et al. Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate. Nat Genet 2009;41 ;619-24.
28. Olivier M, Hollstein M, Hainaut RTP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol 20IO;2:aOOI008.
29. Dong JT Prevalent mutations in prostate cancer. J Cell Biochem 2006;97: 433-47.
30. Shen MM, Abate-Shen C. Molecular genetics of prostate cancer: New prospects for old challenges. Genes Dev 2010:24; 1967-2000.
31. Yoshimoto M, Joshua AM, CunhalW, Coudry RA Fonseca FR Ludkovski O, et al. Absence of TMPRSS2:ERG fusions and PTEN losses in prostate cancer is associated with a favorable outcome. Mod Pathol 2008;21:1451-60.
32. Abate-Shen C, Shen MM, Geimann E. Integrating differentiation and cancer: the Nkx3. l homeobox gene in prostate organogenesis and carcinogenesis. Differentiation 2008:76:717-27. (Pubitemid 352032747)
33. CostaVU Henrique RJeronimo C Epigenetic markers for molecular detection of prostate cancer. Dis Markers 2007. 23.31-41. (Pubitemid 46333639)
34. Hopkins TG, Burns PA Routledge MN. DNA methylation of GSTPI as biomarker in diagnosis of prostate cancer. Urology 2007;69:11-6. (Pubitemid 46201664)
35. Humphrey PA Diagnosis of adenocarcinoma in prostate needle biopsy tissue, j Clin Pathol 2007:60:35-42.
36. Day JRJost M, Reynolds MA Groskopf J, Rittenhouse H. PCA3: from basic molecular science to the clinical lab. Cancer Lea 2011:301:1-6.
37. ErnstT Hergenhahn M, Kenzelmann M, Cohen CD Bonrouhi M. Weninger A et al. Decrease and gain of gene expression are equally discriminatory markers for prostate c arc i no ma: A gene expression analysis on total and microdissected prostate tissue. Am j Pathol 2002; 160:2169-80. (Pubitemid 34663408)
38. Vanaja DK, Cheville JC, Iturria Sj, Young CYTranscriptional silencing of zinc finger protein 185 identified by expression profiling is associated with prostate cancer progression. Cancer Res 2003:63:3877-82. (Pubitemid 36917897)
39. Petrovics G, Liu A, Shaheduzzaman S, Furusato B, SunC, Chen Yet al. Frequent overexpression of ETS-reiated gene-1 (ERG I) in prostate cancer trans criptome. Oncogene 2005;24:3847-52. (Pubitemid 40826884)
40. Tomlins SA Rhodes DR Perner S, Dhanasekaran SM, Mehra R, Sun XW, et al. Recurrent fusion ofTMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005:310:644-8. (Pubitemid 41528150)
41. Svensson MA LaFargue Cj, MacDonaidTY Pflueger D, Kitabayashi N, Santa-Cruz AM, et al. Testing mutual exclusivity of ETS rearranged prostate cancer. Lab Invest 2011;91:404-12.
42. Wang Q, U W, Liu XS, Carroll JS, janne OA Keeton EK, et al. A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth. Mol Cell 2007:27:380-92. (Pubitemid 47126935)
43. Lin B, Ferguson C. White JT. Wang S. Vessella RTrue LD, et al. Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2. Cancer Res 1999;59:4180-4. (Pubitemid 29418721)
44. Vaaraia MH. Porvari KS, Kellokumpu S. Kronen ARVihko FT. Expression of transmembrane serine protease TMPRSS2 in mouse and human tissues. J Pathol 2001;193:134-40. (Pubitemid 32051123)
45. Mani RS, Tomlins SA Callahan K, Ghosh A Nyati MK, Varambally S, et al. Induced chromosomal proximity and gene fusions in prostate cancer. Science 2009;326:1230.
46. Lin C. Yang LTanasa B, Hutt K, Ju BG, Ohgi K, et al. Nuclear receptor-induced chromosomal proximity and DNA breaks underlie specific translocations in cancer. Ceil 2009; 139:1069-83.
47. Haffner MC Aryee MJ Toubaji A Esopi DM. AIbadine R. Gurel B. et al. Androgen-inducedTOP2B-mediated double-strand breaks and prostate cancer gene rearrangements. Nat Genet 2010;42;668-75.
48. Clark JR Cooper CS. ETS gene fusions in prostate cancer. Nat Rev Urol, 2009;6:429-39.
49. Reddy ES, RaoVN. PapasTS. The ERG gene: A 2 human gene related to the ets oncogene. Proc Natl Acad Sci U SA 1987;84:6131-5. (Pubitemid 17140179)
50. Rao VN, Papas TS, Reddy ES. ahumanets-re!atedgcneonchromosome 2l; alternative splicing, polyadenyiation, and translation. Science 1987:237:635-9. (Pubitemid 17118724)
51. Watson DK Turner DR Scheiber MN, FindIay VJ. Watson PM, ETS transcription factor expression and conversion during prostate and breast cancer progression. Open Cancer j 2010;3:24-39.
52. Seth A Watson DK. Ets transcription factors and their emerging roles in human cancer. Eur j Cancer 2005;41:2462-78. (Pubitemid 41540623)
53. Owczarek CM. Portbury Kj, Hardy MR O'Leary DA Kudoh j, Shibuya K. et al. Detailed mapping of the ERG-ETS2 interval of human chromosome 21 and comparison with the region of conserved synteny on mouse chromosome 16. Gene 2004;324:65-77. (Pubitemid 38030326)
54. Hewett FW, Nishi K, Daft EL Clifford Murray J. Selective expression of ERG isoforms in human endothelial cells, intj Biochem Ceil Bio! 2001:33:347-55. (Pubitemid 32324003)
55. D uter que-Coqui I laud M, Niel C, Plaza S, Stehelin D. New human ERG isoforms generated by alternative splicing are transcriptional activators. Oncogene 1993;8:1865-73. (Pubitemid 23212420)
56. Wei GH, Badis G, Berger MR KiviojaT, Palin K, Enge M, et al. Genome-wide analysis of ETS-farnily DN A-binding in vitro and in vivo. Embo j 2010;29:2147-60.
57. Vlaeminck-GuillemV, Carrere S. Dewitte R Stehelin D, Desbiens X. Duterque-Coquillaud M. The Ets family member ERG gene is expressed in mesodermal tissues and neural crests at fundamental steps during mouse embryogenesis. MechDev2GQ0;9!:33i-5.
58. MohamedAATan SH, Mikhalkevich N, Ponniah S. VasioukhinV, Bieberich CJ, et al. Ets family protein, ERG expression in developing and adult mouse tissues by a highly specific monoclonal antibody. J Cancer 2010;1:197-208.
59. Anderson MK. At the crossroads: diverse roles of early thymocyte transcriptional regulators. Immunol Rev 2006;209:191-211.
60. Rivera RR Stuiver MH, Steenbergen R Murre C. Ets proteins: new factors that regulate immunoglobulin heavy-chain gene expression. Mol Cell Biol 1993;13:7163-9. (Pubitemid 23321168)
61. McLaughlin FLudbrookVj, Cox j, von Cariowitz I, Brown S, Randi AM. Combined genomic and antisense analysis reveals that the transcription factor ERG is implicated in endothelial cell differentiation. Blood 2001 ;98;3332-9.
62. Birdsey GM, Dryden NH. Amsellem V, Gebhardt F Sahnan K, Haskard DO, et al. Transcription factor ERG regulates angiogenesis and endothelial apoptosis through VE-cadherin. Blood 2008; 111:3498-506.
63. Iwamoto M. TamamuraY Koyama E, Komori T. Takeshita N, Williams JA et al. Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis. Dev Biol 2007;305:40-51. (Pubitemid 46589406)
64. Anderson MK. Hernandez-Hoyos G, Diamond RA RothenbERGEV Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage. Development 1999;126:3131-48. (Pubitemid 29378177)
65. Maroulakou IG, Bowe DB. Expression and function of Ets transcription factors in mammalian development a regulatory network. Oncogene 2000; 19:6432-42. (Pubitemid 32108433)
66. Wang J, Cai Y Yu W, Ren C, Spencer DM, Ittmann M. Pleiotropic biological activities of alternatively splicedTMPRSS2/ERG fusion gene transcripts. Cancer Res 2008;68:8516-24.
67. Dherdain R Dewitte F, Desbiens X, Stehelin D, Duterque-Coquiliaud M. Mesodermal expression of the chicken ERG gene associated with precartilaginous condensation and cartilage differentiation. Mech Dev 1995;50:17-28.
68. Baltzinger M, Mager-Heckel AM, Remy R XI erg: expression pattern and overexpression during development plead for a role in endothelial cell differentiation. Dev Dyn 1999;216:420-33.
69. Pham VN, Lawson ND, Mugford JW, Dye L Castranova D, Lo B, et al. Combinatorial function of ETS transcription factors in the developing vasculature. Dev Biol 2007;303:772-83. (Pubitemid 46341274)
70. Loughran SJ, Kruse EA Hacking DR de Graaf CA Hyland CD, Willson TA et al. The transcription factor ERG is essentia! for definitive hematopoiesis and the function of adult hematopoietic stem cells. Nat Immunol 2008:9:810-9. (Pubitemid 351859165)
71. Sun C Dobi A Mohamed A Li H Jhangapazham RL Furusato B, et al. TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation. Oncogene 2008;27:5348-53.
72. Yuan L Nikoiova-Krstevski V, Zhan Y, Kondo M, Bhasin M, Varghese L, et al. Antiinflammatory effects of the E!S factor ERG in endothelial cells are mediated through transcript]ana! repression of the interleukin-8 gene. Ore Res 2009;104:1049-57.
73. Pimanda JE. Chan WY Donaldson IJ, Bowen M. GreenAR, Gottgens B. Endogiin expression in the endothelium is regulated by Hi-1, Erg, and Elf-1 acting on the promoter and a-8-kb enhancer. Blood 2006; 107:4737-45. (Pubitemid 43882624)
74. ImYH, Kim HT, Lee C, Poulin D. Welford S, Sorensen PH, et al. EWS-FUI, EWS-ERG, and EWS-ETVI oncoproteins of Ewing tumor family all suppress transcription of transforming growth factor beta type II receptor gene. Cancer Res 2000:60:1536-40. (Pubitemid 30183421)
75. Taoudi S, Bee T Hilton A Knezevic K, Scott J. Willson TA et al. ERG dependence distinguishes developmental control of hematopoietic stem cell maintenance from hematopoietic specification. Genes Dev 2011 ;25:251-62.
76. Ng AR Loughran SJ, Metcalf D, Hyland CD, de Graaf CA HuY et al. ERG is required for self-renewal of hematopoietic stem cells during stress hematopoiesis in mice. Blood 2011;118:2454-61.
77. Nikoiova-Krstevski V Yuan L Le Bras A Vijayaraj R Kondo M, Gebauer I, et al. ERG is required for the differentiation of embryonic stem cells along the endothelial lineage. BMC Dev Biol 2009;9:72.
78. Wang J, Cai Y, Yu W, Ren C, Spencer DM, Ittmann M. Pleiotropic biological activities of alternatively splicedTMPRSS2/ERG fusion gene transcripts. Cancer Res 2008;68:8516-24.
79. Nam RK, Sugar L, Yang W, Srivastava S, Klotz LH, Yang LY et al. Expression of theTMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer. Br j Cancer 2007:97:1690-5. (Pubitemid 350249347)
80. Clark JR Munson KW, Gu jW. Lamparska-Kupsik K, Chan KG, Yoshida jS, et al. Performance of a single assay for both type III and type VITMPRSS2: ERG fusions in noninvasive prediction of prostate biopsy outcome. Clin Chem 2008;54:2007-17. (Pubitemid 352774034)
81. Hu Y Dobi A Sreenath T Cook C. Tadase AY Ravindranath L et al. Delineation of TMPRSS2-ERG splice variants in prostate cancer. Clin Cancer Res 2008;14:4719-25.
82. Furusato B. Gao CU Ravindranath U Chen Y Cullen J, Mc Leod DG, et al. Mapping ofTMPRSS2-ERG fusions in the context of multi-focal prostate cancer. Mod Pathol 2008:21:67-75. (Pubitemid 351172158)
83. Gopaian A Leversha MA Satagopan JM. Zhou Q. A-Ahrnadie HA Fine SW, et al. TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy. Cancer Res 2009:69:1400-6.
84. Clark J, Merson S, Jhavar S, Flohr R Edwards S, Foster CS, et al. Diversity of TMPRSS2-ERG fusion transcripts in the human prostate. Oncogene 2007;26:2667-73. (Pubitemid 46632014)
85. Furusato B, Shaheduzzaman S, Petrovics G, Dobi A Seifert M, Ravindrnnath L et al. Transcriptome analyses of benign and malignant prostate epithelial cells in formal in-fixed paraffin-embedded whole-mounted radical prostatectomy specimens. Prostate Cancer Prostatic Dis 2008: M: 194-7. (Pubitemid 351676610)
86. Andreoiu M, Cheng L Multifocal prostate cancer: biologic, prognostic, and therapeutic implications. Hum Pathol 2010;41:781-93.
87. King JC, Xu j, Wongvipat j, Hieronymus H, Carver BS, Leung DH, et al. Cooperativity ofTMPRSS2-ERG with PI3-kinase pathway activation in prostate oncogenesis. Nat Genet 2009:41:524-6.
88. Hart AH, Corrick CM, Tymms Mj, Hertzog Pj, Kola I. Human ERG is a proto-oncogene with mitogenic and transforming activity. Oncogene 1995:10:1423-30.
89. Sementchenko VI, Schweinfest CW, Papas TS, Watson DK. ETS2 function is required to maintain the transformed state of human prostate cancer cells. Oncogene 1998:17:2883-8. (Pubitemid 29010058)
90. Oikawa T. Yamada T. Molecular biology of the Ets family of transcription factors. Gene 2003:303:1!-34.
91. Rainis U Toki T, Rmanda JE, Rosenthal E, Machol K, Strehl S, et al. The proto-oncogene ERG in megakaryoblastic leukemias. Cancer Res 2005;65:7596-602. (Pubitemid 41297231)
92. Ng AR Hyland CD Metcalf D, Carmichael CL, Loughran SJ, Di Rago L, et al. Trisomy of ERG is required for mye I ©proliferation in a mouse model of Down syndrome. Blood 2010;! E5:3966-9.
93. Stankiewicz MJ. Crispino JD. ETS2 and ERG promote megakaryopoiesis and synergize with alterations in GATA-1 to immortalize hematopoietic progenitor cells. Blood 2009; 113:3337-47.
94. Saek-Adakani S, Smooha G. de Boer J, Scbirc NJ, Morrow M, Rainis L et al. ERG is a megakaryocyte oncogene. Cancer Res 2009;69:4665-73.
95. Marcucci G, Maharry K. Whitman SR Vukosavljevic T, Paschka R Langer C, et al. igh expression levels of the ETS-relatedgene, ERG, predict adverse outcome and improve molecular risk-based classification of cytogenetic ally normal acute myeloid leukemia: a Cancer and Leukemia Group B Study. J Clin Oncol 2007;25:3337-43. (Pubitemid 47325620)
96. Sorensen PH. Lessnick SL, Lopez-Terrada D Liu XF. TricheT], Denny CT. A second Ewing's sarcoma translocation, t(21 ;22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nat Genet i 994;6:146-51.
97. Watson DK, Smyth FE, Thompson DM, Cheng JQ, Testa JR Papas TS, et al. The ERGB/Ri-i gene; isolation and characterization of a new member of the family of human ETS transcription factors. Cell Growth Differ 1992:3:705-13.
98. Ichikawa H. Shimizu K, Hayashi Y Ohki M. An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t( 16;21) chromosomal translocation. Cancer Res 1994;54:2865-8. (Pubitemid 24187764)
99. Tomlins SA Laxman B, Varambay S, Cao X. Yu J. Heigeson BE. et al. Role of theTMPRSS2-ERG gene fusion in prostate cancer. Neoplasia 2008; 10:177-88. (Pubitemid 351240884)
100. Buttice G, Duterque-Coquillaud M. Basuyaux JR Cairere S, Kurkinen M, Stehelin D. Erg, an Ete-family member, differentially regulates human collagcnase I (MMPI) and stromelysinl (MMP3) gene expression by physically interacting with the Fos/jun complex Oncogene 1996; 13:2297-306. (Pubitemid 27026012)
101. KlezovitchO, Risk M, Coleman I, Lucas jM, Null M, True LD et al. A causal role for ERG in neoplastic transformation of prostate epithelium. Proc Natl Acad Sci USA 2008;105:2105-10. (Pubitemid 351439472)
102. Cai J, Kandagatia R Singareddy R Kropinski A Sheng S, Cher ML et al. Androgens Induce Functional CXCR4 through ERG Factor Expression inTMPRSS2-ERG Fusion-Positive Prostate Cancer Cells. Trans! Oncol 2010;3:195-203.
103. Flajollet S. Tian TY Rourens A Tomavo N. Villers A Bonnelye E, et al. Abnormal expression of the ERG transcription factor in prostate cancer cells activates osteopontin. Mol Cancer Res 2011:9:914-24.
104. Thalmann GN, Sikes RA Devoll RE, Kiefer JA Markwalder R Klima I, et al. Osteopontin: possible role in prostate cancer progression. Clin Cancer Res 1999;5:2271-7. (Pubitemid 29399287)
105. Nelson WG. De Marzo AM, Yegnasubramanian S. Epigenetic alterations in human prostate cancers. Endocrinology 2009;150:3991-4002.
106. Kunderfranco P, Mello-Grand M. Cangemi R Pellini S, Mensah A A Jbertini V et al. ETS transcription factors control transcription of EZH2 and epigenetic silencing of the tumor suppressor gene Nkx3. l in prostate cancer. PLoS ONE 20IO;5:el0547.
107. Dobi A Thangapazham R Srivastava S, Conservation of NKX binding sites within theTMPRSS2 promoter and hormone regulation of the ERG gene expression in prostate cancer (Abstract). In: Proceedings of the 99th Annual Meeting of the American Association for Cancer Research. Apr 12-16, 2008; San Diego, CA Poster# 60, 2008.
108. Abbas A, Gupta S. The role of histone deacetylases in prostate cancer. Epigenetics 2008:3:300-9.
109. Gupta S, lljin K, Sara H, Mpindi JR MirttiT. Vainio R et al. FZD4 as a mediator of ERG oncogene-induced WNT signaling and epithelial-to-mesenchymai transition in human prostate cancer cells. Cancer Res, 2010;70:6735-45.
110. Fortson WS, Kayarthodi S, FujimuraXXu H, Matthews R Grizzle WE, et al. Histone deacetylase inhibitors, valproic acid and trichostatin-A induce apoptosis and affect acetylation status of p53 in ERG-positive prostate cancer cells. Int j Oncol 20M;39:!M-9.
111. Leshem O, Madar S, Kogan-Sakin I, Kamer I, Goldstein I, Brosh R et al. TMPRSS2/ERG promotes epithelial to mesenchymal transition through the ZEBI/ZEB2 axis in a prostate cancer model. PLoS ONE 2011;6:e2l650.
112. Thiery JR Acioque H, Huang BY Nieto MA Epithelial-mesenchymal transitions in development and disease. Cell 2009; 139:871-90.
113. Mochmann LH. Bockj, Qrtiz-Tanchez J, Schlee C, Bohne A Neumann K, et al. Genome-wide screen reveals WNT II. a non-canonical WNT gene, as a direct target of ETS transcription factor ERG. Oncogene 2011 ;30:2044-56.
114. Zhu H. Mazor M, Kawano Y Waiker MM. Leung HY Armstrong K, et al. Analysis of Wnt gene expression in prostate cancer: mutual inhibition by WNT 11 and the androgen receptor. Cancer Res 2004;64:7918-26. (Pubitemid 39446925)
115. Uysai-Onganer R KawanoY Caro M, Waiker MM, Diez S, Darrington RS, et al. Wnt-i I promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells. Mol Cancer 2010;9:55.
116. Drake JM, Strohbehn G, Bair TB, Moreland JG, Henry MD ZEBI enhances transendothelial migration and represses the epithelial phenotype of prostate cancer cells. Mol Biol Cell 2009;20:2207-17.
117. Wang J, Cai Y Shao LJ, Siddiqui J, Palanisamy N, Li R, et al. Activation of NF-{kappa}B by TMPRSS2/ERG Fusion Isoforms through Toll-Like Receptor-4. Cancer Res 2011:71:1325-33.
118. Mohamed AA Tan SH. Sun C Shaheduzzaman S, Hu Y Petrovics G, et al. ERG oncogene modulates prostaglandin signaling in prostate cancer cells. Cancer Biol Ther 2011; 11:410-7.
119. Brenner JC. Ateeq B, Li Y Yocum AK, Cao Q. Asangani IA et al. Mechanistic rationale for inhibition of po(y(ADP-ribose) polymerase in ETS gene fusion-positive prostate cancer. Cancer Cell 2011; 19:664-78.
120. Korenchuk S, Lehr JE, MClean L Lee YG, Whitney S. Vessella R et al. VCaRa cell-based model system of human prostate cancer, in Vivo 2001:15:163-8. (Pubitemid 32328191)
121. ZongY, Xin L, Goldstein AS, Lawson DA Teitell MA Witte ON. ETS family transcription factors collaborate with alternative signaling pathways to induce carcinoma from adult murine prostate cells. Proc Natl Acad Sci USA 2009;106:12465-70.
122. Taylor BS, Schultz N, Hieronymus H, Gopalan A Xiao Y, Carver BS, et al. Integrative genomic profiling of human prostate cancer. Cancer Cell 2010;18:11-22.
123. Netto GJ, Epstein Jl. Theranostic and prognostic biomarkers: genomic applications in urologica! malignancies. Pathology 2010:42:384-94.
124. Netto GJ. Molecular diagnostics in urologic malignancies: a work in progress. Arch Pathol Lab Med 2011;135:610-21.
125. Rowley JD. Chromosomes in leukemia and beyond: from irrelevant to central piayers. Annu Rev Genomics Hum Genet 2009;10:1-18.
126. Rubin MA Maher CA Chinnaiyan AM. Common gene rearrangements in prostate cancer, J Clin Oncol 2011:29:3659-68.
127. Leman ES, GetzenbERGRH. Biomarkers for prostate cancer. J Cell Biochem 2009;108:3-9.
128. Perner S, Demichelis R Beroukhim R, Schmidt FH, Mosquera JM, Setlur S, et al. TMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. Cancer Res 2006:66:8337-41. (Pubitemid 44449140)
129. Yaskiv Q Zhang X, Simmerman K, Daly T, He H, Falzarnno S, et al. The utility of ERG/P63 double immunohistochemical staining in the diagnosis of limited cancer in prostate needle biopsies. Am j Surg Pathol 2011:35:1062-8.
130. Attard G. de Bono JS. Ciark J, Cooper CS. Studies of TMPRSS2-RGgene fusions in diagnostic trans-rectal prostate biopsies. Gin Cancer Res 2010; 16:1340.
131. Mosquera JM, Mehra R, Regan MM, Perner S, Genega EM, Bueti G, et al. Prevalence of [ MPRSS2-ERG fusion prostate cancer among men undergoing prostate biopsy in the United States. Clin Cancer Res 2009;15:4706-11.
132. Demichelis E Fall K, Perner S. Andren O, Schmidt R Setlur SR, et al. TMPRSS 2: ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene 2007;26:4596-9. (Pubitemid 47037039)
133. Saramaki OR, Harjula AE, Martikainen PM. Vessella RL, Tammela TLVisakorpi T. TMPRSS2:ERG Fusion Identifies a Subgroup of Prostate Cancers with a Favorable Prognosis. Clin Cancer Res 2008; 14:3395-400.
134. Winnes M, Lissbrant E, Damber JE, Stenman G. Molecular genetic analyses of theTMPRS52-ERG andTMPRSS2-ETVI gene fusions in 50 cases of prostate cancer. Oncol Rep 2007; 17: i 033-6.
135. Dobi A Furusato B, Shaheduzzaman S, ChenYVahey M, NydernT, e d. ERG Expression Levels in Prostate Tumors Reflect Functional Status of the Androgen Receptor (AR) as a Consequence of Fusion of ERG with AR Regulated Gene Promoters. Open Cancer J 2010;3: 101-8.
136. Boormans JL, Porkka K, Visakorpi T, Trapmanj. Confirmation of the association of TMPRSS2(exon 0):ERG expression and a favorable prognosis of primary prostate cancer. Eur Urol 2011;60:183-4.
137. Minner S, Enodien M, Sirma H, Luebke AM, Krohn A Mayer PS et.al. ERG Status Is Unrelated to PSA Recurrence in Radically Operated Prostate Cancer in the Absence of Antihormona!Therapy. Clin Cancer Res 201 i; 17:5878-88
138. Furusato B. Tan SH. Young D, Dobi A Sun C, Mohamed Aeal. ERG oncoprotein expression in prostate cancer: clonal progression of ERG-positive tumor cells and potential for ERG-based stratification. Prostate Cancer Prostatic Dis 2010; 13:228-37.
139. Squire JATMPRSS2-ERG and PTEN loss in prostate cancer. Nat Genet 2009;41:509-10.
140. Laxman B, Morris DS. Yu J, Siddiqui J, Cao J, Mehra R et al. A first-generation multiplex biomarker analysis of urine for the early detection of prostate cancer. Cancer Res 2008;68:645-9. (Pubitemid 351206738)
141. Rice KR Chen Y. Ali A Whitman EJ, Blase A Ibrahim M, et al. Evaluation of the ETS-related gene mRNA in urine for the detection of prostate cancer. Clin Cancer Res 2010;16:1572-6.
142. Tomlins SA Aubin SM, Siddiqui J, Lonigro RJ, Sefton-Miller L, Miick S, et al. Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA Sci Transl Med 2011 ;3:94ra72.
143. van Gils MP, Hessels D, Peelen WRVergunst H, Mulders PF Schalken JA Preliminary evaluation of the effect of dutasteride on PCA3 in post-DRE urine sediments; a randomized, open-label, para!! el-group pilot study. Prostate 2009;69:1624-34.
144. Hessels D van Gils MR van Hooij O. Jannink SA Witjes JA Verhaegh GW, et al. Predictive value of PCA3 in urinary sediments in determining clinico-pathological characteristies of prostate cancer. Prostate 2010;70:10-6.
145. Lee GL, Dobi A Srivastava S. Prostate cancer: diagnostic performance of the PCA3 urine test Nat Rev Urol 201 I ;8:123-4.
146. McLeod DG. Dobi A Words of wisdom. Re: Antibody-Based Detection of ERG Rearrangement-Positive Prostate Cancer. Eur Urol 201 l;60:l-123.
147. Falzarano SM. Zhou M. Carver R Tsuzuki T. Simmerman K. He H, et al. ERG gene rearrangement status in prostate cancer detected by immunohistochemistry. Virchows Arch 2011;459:441-7.
148. Miettinen M, Wang ZR Paetau A Tan SH, Dobi A Srivastava S, et al. ERG transcription factor as an immunohistochemical marker for vascular endothelial tumors and prostatic carcinoma. Am j Surg Pathol 201 l;35:432-4l.
149. Erkizan HV Kong Y Merchant M. Schlottmann S, Barber-RotenbERG JS, Yuan L, et al. A small molecule blocking oncogenic protein EWS-FLM interaction with RNA heiicase A inhibits growth of Ewing's sarcoma. Nat Med 2009;15:750-6.
150. Rahim S, Beauchamp EM, KongY Brown MLToretsky JA, Uren AYK-4-279 inhibits ERG and ETVI mediated prostate cancer cell invasion. PLoS ONE 20ll;6:el9343.
151. Khan N, Jeffers M, Kumar S, Hackett C, Boldog R Khramtsov N. Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. Biochem j 2008;409:581-9.
152. Rouleau M. Patel A Hendze! Mj, Kaufmann SH. Poirier GG. PARP inhibition: PARPi and beyond. Nat Rev Cancer 2010; 10:293-301.
153. Leung M, Rosen D, Fields S, Cesano A Budman DR. Poly(ADP-ribose) polymerase-! inhibition: preclinical and clinical development of synthetic lethality. Mol Med 201!: 17:854-62.
154. Sandhu SK. YapTA de Bono JS. The Emerging Role of Poly(ADP-Ribose) Polymerase Inhibitors inCancerTreatment. Curr DrugTargets 2011. [In Press]
155. Prido C, OhWK, Loda M. Novel therapeutic strategies in prostate cancer: establishing a stratification system for patient selection in targeted trials. I Drugs 2009; 12: 165-8.
156. Mostaghel EA Montgomery B, Nelson PS. Castration-resistant prostate cancer: targeting androgen metabolic pathways in recurrent disease. Urol Oncol 2009;27:251-7.