Cooperativity of TMPRSS2-ERG with PI3-kinase pathway activation in prostate oncogenesis.
The TMPRSS2-ERG fusion, present in approximately 50% of prostate cancers, is less common in prostatic intraepithelial neoplasia (PIN), raising questions about whether TMPRSS2-ERG contributes to disease initiation. We identified the translational start site of a common TMPRSS2-ERG fusion and showed that transgenic TMPRSS2-ERG mice develop PIN, but only in the context of PI3-kinase pathway activation. TMPRSS2-ERG-positive human tumors are also enriched for PTEN loss, suggesting cooperation in prostate tumorigenesis.
King
Jennifer C
JC
Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Xu
Jin
J
Wongvipat
John
J
Hieronymus
Haley
H
Carver
Brett S
BS
Leung
David H
DH
Taylor
Barry S
BS
Sander
Chris
C
Cardiff
Robert D
RD
Couto
Suzana S
SS
Gerald
William L
WL
Sawyers
Charles L
CL
D000818:Animals; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction
D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D019869:Phosphatidylinositol 3-Kinases