Source:http://linkedlifedata.com/resource/pubmed/id/10969813
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
16
|
| pubmed:dateCreated |
2000-9-14
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| pubmed:abstractText |
Azoxymethane (AOM)-induced colonic carcinogenesis involves a number of mutations, including those in the K-ras gene and CTNNB1, that codes for beta-catenin. Prior in vitro studies have also demonstrated that wild type p21(K-ras) can be activated by epigenetic events. We identified 15 K-ras mutations in 14 of 84 AOM-induced colonic tumors by three independent methods. By single strand conformational polymorphism, we also observed mutations in 22 of 68 tumors in exon 3 of CTNNB1. A highly sensitive method was then used to measure p21ras activation levels. All tumors assayed possessing K-ras mutations had significantly higher p21ras activation levels (8.8 +/- 1.5%; n = 13) compared with that of control colon (3.7 +/- 0.4; n = 6; P < 0.05) or tumors without such mutations (4.2 +/- 0.4%; n = 70; P < 0.05). Among tumors with wild-type K-ras, there was a subset of tumors (18 of 70) that had significantly higher p21ras activation levels (8.0 +/- 0.9%; n = 18) compared with control colons. In three of four tumors examined with activated wild-type p21ras, we observed increased c-erbB-2 receptor expression and decreased Ras-GAP expression. In contrast, only one of eight tumors examined with wild-type ras and nonactivated p21ras demonstrated these alterations. Mitogen-activated protein kinase (MAPK) activation and cyclooxygenase-2 (COX-2) expression were increased in tumors with mutated or activated wild-type p21ras, compared with their nonactivated counterparts. Although beta-catenin mutations did not alter COX-2 expression or MAPK activity, mutations in either K-ras or beta-catenin significantly increased cyclin D1 expression. In contrast, in tumors with wild-type but activated p21-ras, cyclin D1 expression was not enhanced. Thus, the spectrum of changes in MAPK, COX-2, and cyclin D1 is distinct among tumors with ras or beta-catenin mutations or nonmutational activation of p21ras.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Azoxymethane,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens,
http://linkedlifedata.com/resource/pubmed/chemical/Catnb protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins p21(ras),
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0008-5472
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
|
| pubmed:volume |
60
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4602-9
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:10969813-Animals,
pubmed-meshheading:10969813-Azoxymethane,
pubmed-meshheading:10969813-Carcinogens,
pubmed-meshheading:10969813-Colonic Neoplasms,
pubmed-meshheading:10969813-Cyclin D1,
pubmed-meshheading:10969813-Cyclooxygenase 2,
pubmed-meshheading:10969813-Cytoskeletal Proteins,
pubmed-meshheading:10969813-Enzyme Activation,
pubmed-meshheading:10969813-Genes, ras,
pubmed-meshheading:10969813-Isoenzymes,
pubmed-meshheading:10969813-Male,
pubmed-meshheading:10969813-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:10969813-Mutation,
pubmed-meshheading:10969813-Polymorphism, Restriction Fragment Length,
pubmed-meshheading:10969813-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:10969813-Proto-Oncogene Proteins p21(ras),
pubmed-meshheading:10969813-Rats,
pubmed-meshheading:10969813-Rats, Inbred F344,
pubmed-meshheading:10969813-Trans-Activators,
pubmed-meshheading:10969813-beta Catenin
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| pubmed:year |
2000
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| pubmed:articleTitle |
Mutational and nonmutational activation of p21ras in rat colonic azoxymethane-induced tumors: effects on mitogen-activated protein kinase, cyclooxygenase-2, and cyclin D1.
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| pubmed:affiliation |
University of California, San Diego 92093, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|