title: Epithelial Pten is dispensable for intestinal homeostasis but suppresses adenoma development and progression after Apc mutation.
abstract: PTEN acts as a tumor suppressor in a range of tissue types and has been implicated in the regulation of intestinal stem cells. To study Pten function in the intestine, we used various conditional transgenic strategies to specifically delete Pten from the mouse intestinal epithelium. We show that Pten loss specifically within the adult or embryonic epithelial cell population does not affect the normal architecture or homeostasis of the epithelium. However, loss of Pten in the context of Apc deficiency accelerates tumorigenesis through increased activation of Akt, leading to rapid development of adenocarcinoma. We conclude that Pten is redundant in otherwise normal intestinal epithelium and epithelial stem cells but, in the context of activated Wnt signaling, suppresses progression to adenocarcinoma through modulation of activated Akt levels.
authors.affiliation: Cardiff School of Biosciences, Cardiff University, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Marsh
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Winton
authors.forename: Geraint T
authors.initials: GT
authors.lastname: Williams
authors.forename: Nicole
authors.initials: N
authors.lastname: Dubois
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Sansom
authors.forename: Alan R
authors.initials: AR
authors.lastname: Clarke
mesh_terms: D000236:Adenoma / Q000139:chemically induced / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000818:Animals; D017353:Gene Deletion; D007414:Intestinal Neoplasms / Q000235:genetics*; D007421:Intestine, Small / Q000473:pathology*; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D013629:Tamoxifen; D019324:beta-Naphthoflavone
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D013629:Tamoxifen; D019324:beta-Naphthoflavone; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse