Article abstract
Nature Genetics 40, 1436 - 1444 (2008)
Published online: 16 November 2008 | doi:10.1038/ng.256
Epithelial Pten is dispensable for intestinal homeostasis but suppresses adenoma development and progression after Apc mutation
Victoria Marsh1, Douglas J Winton2, Geraint T Williams3, Nicole Dubois4,6, Andreas Trumpp4,6, Owen J Sansom5 & Alan R Clarke1
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.
- Cardiff School of Biosciences, Cardiff University, CF10 3US, UK.
- Cambridge Research Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
- Wales College of Medicine, Cardiff University, CF14 4XN, UK.
- Ecole Polytechnique Fédérale de Lausanne, Swiss Institute for Experimental Cancer Research, School of Life Science, CH-1066 Epalinges, Switzerland.
- The Beatson Institute, Garscube Estate, Glasgow G61 1BD, UK.
- Present addresses: McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario M5G 1L7, Canada (N.D.) and Division of Cell Biology, Deutsches Krebsforschungszentrum (DKFZ) DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany (A.T.).
Correspondence to: Owen J Sansom5 e-mail: o.sansom@beatson.gla.ac.uk
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