Epithelial Pten is dispensable for intestinal homeostasis but suppresses adenoma development and progression after Apc mutation

Victoria Marsh, Douglas J. Winton, Geraint T. Williams, Nicole Dubois, Andreas Trumpp, Owen J. Sansom, Alan R. Clarke

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

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.

Original languageEnglish
Pages (from-to)1436-1444
Number of pages9
JournalNature Genetics
Volume40
Issue number12
DOIs
StatePublished - Dec 2008
Externally publishedYes

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