ETS rearrangements and prostate cancer initiation.
The first recurrent translocation event in prostate cancer has been recently described; it results in the translocation of an ETS (E26 transformation specific) transcription factor (ERG or ETV1) to the TMPRSS2 promoter region, which contains androgen responsive elements. The TMPRSS2:ERG genetic rearrangement has been reported to occur in approximately 40% of primary prostate tumours (ETV1 genetic rearrangements occur at a much lower frequency), and it results in the aberrant androgen-regulated expression of ERG. Tomlins et al. concluded that ETS genetic rearrangements are sufficient to initiate prostate neoplasia. However, here we show that ETS genetic rearrangements may in fact represent progression events rather than initiation events in prostate tumorigenesis. To this end, we demonstrate that the prostate-specific overexpression of ERG does not initiate prostate tumorigenesis.
Carver
Brett S
BS
Cancer Biology and Genetics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Tran
Jennifer
J
Chen
Zhenbang
Z
Carracedo-Perez
Arkaitz
A
Alimonti
Andrea
A
Nardella
Caterina
C
Gopalan
Anuradha
A
Scardino
Peter T
PT
Cordon-Cardo
Carlos
C
Gerald
William
W
Pandolfi
Pier Paolo
PP
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D015870:Gene Expression; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D000071230:Transcriptional Regulator ERG; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; C531115:ERG protein, mouse; C490641:Etv1 protein, mouse; D015513:Oncogene Proteins; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG