Source:http://linkedlifedata.com/resource/pubmed/id/20110688
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2-3
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pubmed:dateCreated |
2010-1-29
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenomatous Polyposis Coli Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Hormonal,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta,
http://linkedlifedata.com/resource/pubmed/chemical/serum-glucocorticoid regulated...
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pubmed:status |
MEDLINE
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pubmed:issn |
1421-9778
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2010 S. Karger AG, Basel.
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pubmed:issnType |
Electronic
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
271-8
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:20110688-Adenomatous Polyposis Coli Protein,
pubmed-meshheading:20110688-Animals,
pubmed-meshheading:20110688-Antineoplastic Agents, Hormonal,
pubmed-meshheading:20110688-Cell Line,
pubmed-meshheading:20110688-Dexamethasone,
pubmed-meshheading:20110688-Glycogen Synthase Kinase 3,
pubmed-meshheading:20110688-Humans,
pubmed-meshheading:20110688-Immediate-Early Proteins,
pubmed-meshheading:20110688-Intestinal Neoplasms,
pubmed-meshheading:20110688-Mice,
pubmed-meshheading:20110688-Mice, Knockout,
pubmed-meshheading:20110688-Protein-Serine-Threonine Kinases,
pubmed-meshheading:20110688-beta Catenin
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pubmed:year |
2010
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pubmed:articleTitle |
SGK1-dependent intestinal tumor growth in APC-deficient mice.
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pubmed:affiliation |
Department of Physiology, University of Tuebingen, 72076 Tuebingen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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