title: Cooperativity of TMPRSS2-ERG with PI3-kinase pathway activation in prostate oncogenesis.
abstract: 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.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: King
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.forename: John
authors.initials: J
authors.lastname: Wongvipat
authors.forename: Haley
authors.initials: H
authors.lastname: Hieronymus
authors.forename: Brett S
authors.initials: BS
authors.lastname: Carver
authors.forename: David H
authors.initials: DH
authors.lastname: Leung
authors.forename: Barry S
authors.initials: BS
authors.lastname: Taylor
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
authors.forename: Robert D
authors.initials: RD
authors.lastname: Cardiff
authors.forename: Suzana S
authors.initials: SS
authors.lastname: Couto
authors.forename: William L
authors.initials: WL
authors.lastname: Gerald
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sawyers
mesh_terms: 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
chemical_list: D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D019869:Phosphatidylinositol 3-Kinases