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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2010-1-29
pubmed:abstractText
Adenomatous polyposis coli (APC) is inactivated in familial adenomatous polyposis and sporadic colorectal cancer. Mice carrying defective APC (apc(Min/+)) spontaneously develop gastrointestinal tumors. APC binds GSK3beta, which phosphorylates beta-catenin thus fostering its degradation. beta-catenin upregulates the serum- and glucocorticoid-inducible kinase Sgk1, which inhibits GSK3beta. The present study explored the role of SGK1 in tumor growth of apc(Min/+)mice. apc(Min/+)mice were crossed with SGK1-knockout mice (sgk1(-/-)) and their wild type littermates (sgk1(+/+)) generating apc(Min/+)/sgk1(-/-)mice and apc(Min/+)/sgk1(+/+)mice. beta-catenin abundance was determined by Western blotting and confocal microscopy. As a result apc(Min/+)/sgk1(+/+)mice developed significantly more intestinal tumors than apc(Min/+)/sgk1(-/-)mice. Following chemical cancerogenesis, colonic beta-catenin protein abundance was significantly higher in sgk1(+/+)mice than in sgk1(-/-)mice. beta-catenin expression was significantly increased in HEK293 cells treated with dexamethasone for upregulation of Sgk1. In conclusion, SGK1 expression favors the development of intestinal tumors in APC-deficient mice, an effect at least partially due to enhanced beta-catenin protein abundance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1421-9778
pubmed:author
pubmed:copyrightInfo
Copyright 2010 S. Karger AG, Basel.
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
271-8
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
SGK1-dependent intestinal tumor growth in APC-deficient mice.
pubmed:affiliation
Department of Physiology, University of Tuebingen, 72076 Tuebingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't