title: Early onset of neoplasia in the prostate and skin of mice with tissue-specific deletion of Pten.
abstract: PTEN is a tumor suppressor gene mutated in various advanced human neoplasias, including glioblastomas and prostate, breast, endometrial, and kidney cancers. This tumor suppressor is a lipid phosphatase that negatively regulates cell survival and proliferation mediated by phosphatidylinositol 3-kinase/protein kinase B signaling. Using the Cre-loxP system, we selectively inactivated Pten in murine tissues in which the MMTV-LTR promoter is active, resulting in hyperproliferation and neoplastic changes in Pten-null skin and prostate. These phenotypes had early onset and were completely penetrant. Abnormalities in Pten mutant skin consisted of mild epidermal hyperplasia, whereas prostates from these mice exhibited high-grade prostatic intraepithelial neoplasia (HGPIN) that frequently progressed to focally invasive cancer. These data demonstrate that Pten is an important physiological regulator of growth in the skin and prostate. Further, the early onset of HGPIN in Pten mutant males is unique to this animal model and implicates PTEN mutations in the initiation of prostate cancer. Consistent with high PTEN mutation rates in human prostate tumors, these data indicate that PTEN is a critical tumor suppressor in this organ.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Ontario Cancer Institute and University Health Network, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
authors.forename: Stéphanie A
authors.initials: SA
authors.lastname: Backman
authors.forename: Danny
authors.initials: D
authors.lastname: Ghazarian
authors.forename: Kelvin
authors.initials: K
authors.lastname: So
authors.forename: Otto
authors.initials: O
authors.lastname: Sanchez
authors.forename: Kay-Uwe
authors.initials: KU
authors.lastname: Wagner
authors.forename: Lothar
authors.initials: L
authors.lastname: Hennighausen
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.forename: William B
authors.initials: WB
authors.lastname: Chapman
authors.forename: Vuk
authors.initials: V
authors.lastname: Stambolic
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002455:Cell Division; D017931:DNA Primers; D017353:Gene Deletion; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013953:Thymus Neoplasms / Q000235:genetics / Q000473:pathology
chemical_list: D017931:DNA Primers