HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: fj.08-123125v1 23/6/1835    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Langlois, M.-J. Articles by Perreault, N. Search for Related Content PubMed PubMed Citation Articles by Langlois, M.-J. Articles by Perreault, N.

Epithelial phosphatase and tensin homolog regulates intestinal architecture and secretory cell commitment and acts as a modifier gene in neoplasia

Marie-Josée Langlois^*,, Sébastien A. B. Roy^*,, Benoit A. Auclair^*,, Christine Jones^*,, François Boudreau^*,, Julie C. Carrier^*,, Nathalie Rivard^*, and Nathalie Perreault^*,,1

^* Canadian Institutes of Health Research Team on Digestive Epithelium,

Département d’Anatomie et Biologie Cellulaire, and

Département de Médecine, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada

¹Correspondence: Dépt. d’Anatomie et Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, QC, Canada J1H 5N4. E-mail: nathalie.perreault{at}usherbrooke.ca

Phosphatase and tensin homolog (PTEN), a negative regulator of the phosphatidylinositol 3-kinase/Akt pathway, is one of the most frequently mutated/deleted tumor suppressor genes in human cancers. The aim of this study was to gain insight into the role played by PTEN in intestinal homeostasis and epithelial cell function. Using the Cre/loxP system, we have generated a mouse with a conditional intestinal epithelial Pten deficiency. Pten mutant mice and controls were sacrificed for histology, immunofluorescence, Western blot, and quantitative polymerase chain reaction analysis. Our results show that loss of epithelial Pten leads to an intestinalomegaly associated with an increase in epithelial cell proliferation. Histological analysis demonstrated significant perturbation of the crypt-villus architecture, a marked increase in goblet cells and a decrease in enteroendocrine cells, suggesting a role for Pten in the commitment of the multipotential-secretory precursor cell. Loss of epithelial Pten does not result in induction of nuclear β-catenin protein levels, nor is it sufficient to promote tumorigenesis initiation. However, it severely enhances intestinal tumor load in Apc^Min/+ mice, in which c-Myc is already deregulated. These results reveal an unknown function for Pten signaling in the commitment of multipotential-secretory progenitor cells and suggest that epithelial Pten functions as a modifier gene in intestinal neoplasia.—Langlois, M.-J., Roy, S. A. B., Auclair, B. A., Jones, C., Boudreau, F., Carrier, J. C., Rivard, N., Perreault, N. Epithelial phosphatase and tensin homolog regulates intestinal architecture and secretory cell commitment and acts as a modifier gene in neoplasia.

Key Words: phosphatidylinositol 3-kinase • Akt • β-catenin • cell fate • organomegaly • differentiation

This article has been cited by other articles:

				N. Coant, S. Ben Mkaddem, E. Pedruzzi, C. Guichard, X. Treton, R. Ducroc, J. N. Freund, D. Cazals-Hatem, Y. Bouhnik, P. L. Woerther, et al. NADPH Oxidase 1 Modulates WNT and NOTCH1 Signaling To Control the Fate of Proliferative Progenitor Cells in the Colon Mol. Cell. Biol., June 1, 2010; 30(11): 2636 - 2650. [Abstract] [Full Text] [PDF]