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.
Sun
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C
Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Rockville, MD 20852, USA.
Dobi
A
A
Mohamed
A
A
Li
H
H
Thangapazham
R L
RL
Furusato
B
B
Shaheduzzaman
S
S
Tan
S-H
SH
Vaidyanathan
G
G
Whitman
E
E
Hawksworth
D J
DJ
Chen
Y
Y
Nau
M
M
Patel
V
V
Vahey
M
M
Gutkind
J S
JS
Sreenath
T
T
Petrovics
G
G
Sesterhenn
I A
IA
McLeod
D G
DG
Srivastava
S
S
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