TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation.
The high prevalence of TMPRSS2-ERG rearrangements ( approximately 60%) in prostate cancer (CaP) leads to androgenic induction of the ETS-related gene (ERG) expression. However, the biological functions of ERG overexpression in CaP remain to be understood. ERG knockdown in TMPRSS2-ERG expressing CaP cells induced striking morphological changes and inhibited cell growth both in cell culture and SCID mice. Evaluation of the transcriptome and specific gene promoters in ERG siRNA-treated cells and investigation of gene expression signatures of human prostate tumors revealed ERG-mediated activation of C-MYC oncogene and the repression of prostate epithelial differentiation genes (PSA and SLC45A3/Prostein). Taken together, these data combining cell culture and animal models and human prostate tumors reveal that ERG overexpression in prostate tumor cells may contribute to the neoplastic process by activating C-MYC and by abrogating prostate epithelial differentiation as indicated by prostate epithelial specific markers.
Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Rockville, MD 20852, USA.
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Sun
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Dobi
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Mohamed
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Li
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Thangapazham
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Furusato
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Shaheduzzaman
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Tan
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Vaidyanathan
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Whitman
D J
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Hawksworth
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Chen
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Nau
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Patel
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Vahey
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Gutkind
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Sreenath
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Petrovics
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Sesterhenn
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McLeod
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Srivastava
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; C489427:MYC protein, human; D008565:Membrane Proteins; D015514:Oncogene Proteins, Fusion; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C526547:Slc45A3-ETV5 fusion protein, human; C515553:TMPRSS2-ERG fusion protein, human; C422655:prostein; D017430:Prostate-Specific Antigen