| pubmed-article:11884607 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11884607 | lifeskim:mentions | umls-concept:C0007634 | lld:lifeskim |
| pubmed-article:11884607 | lifeskim:mentions | umls-concept:C0014597 | lld:lifeskim |
| pubmed-article:11884607 | lifeskim:mentions | umls-concept:C0242957 | lld:lifeskim |
| pubmed-article:11884607 | lifeskim:mentions | umls-concept:C0929301 | lld:lifeskim |
| pubmed-article:11884607 | lifeskim:mentions | umls-concept:C0006141 | lld:lifeskim |
| pubmed-article:11884607 | lifeskim:mentions | umls-concept:C1510411 | lld:lifeskim |
| pubmed-article:11884607 | lifeskim:mentions | umls-concept:C0079183 | lld:lifeskim |
| pubmed-article:11884607 | lifeskim:mentions | umls-concept:C0221099 | lld:lifeskim |
| pubmed-article:11884607 | pubmed:issue | 7 | lld:pubmed |
| pubmed-article:11884607 | pubmed:dateCreated | 2002-3-8 | lld:pubmed |
| pubmed-article:11884607 | pubmed:abstractText | ErbB2/Neu destabilizes the cyclin-dependent kinase (Cdk) inhibitor p27 and increases expression of cyclin D1. Therefore, we studied the roles of p27 and cyclin D1 in ErbB2-mediated mammary epithelial cell transformation. Overexpression of ErbB2 or cyclin D1 in p27(+/-) primary murine mammary epithelial cells resulted in increased proliferation, cyclin D1 nuclear localization, and colony formation in soft agar compared to those in p27(+/+) cells. In contrast, ErbB2- or cyclin D1-overexpressing p27(-/-) cells displayed reduced proliferation, anchorage-independent growth, Cdk4 activity, cyclin D1 expression, and cyclin D1 nuclear localization compared to wild-type cells. A cyclin D1 mutation in its nuclear export sequence (T286A) partially rescued nuclear localization of cyclin D1 in p27(-/-) cells but did not increase proliferation or Cdk4 kinase activity. Overexpression of E2F1, however, increased proliferation to the same degree in p27(+/+), p27(+/-), and p27(-/-) cells. Mammary glands from MMTV (mouse mammary tumor virus)-neu/p27(+/-) mice exhibited alveolar hyperplasia, enhanced proliferation, decreased apoptosis, and accelerated tumor formation compared to MMTV-neu/p27(+/+) glands. However, MMTV-neu/p27(-/-) glands showed decreased proliferation, cyclin D1 expression, and Cdk4 activity, as well as markedly prolonged tumor latency, compared to MMTV-neu/p27(+/+) glands. These results suggest that p27(+/-) mammary epithelium may be more susceptible to oncogene-induced tumorigenesis, whereas p27-null glands, due to severely impaired cyclin D1/Cdk4 function, are more resistant to transformation. | lld:pubmed |
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| pubmed-article:11884607 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11884607 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11884607 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:11884607 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:11884607 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11884607 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:11884607 | pubmed:issn | 0270-7306 | lld:pubmed |
| pubmed-article:11884607 | pubmed:author | pubmed-author:BrantleyDana... | lld:pubmed |
| pubmed-article:11884607 | pubmed:author | pubmed-author:HamiltonEliza... | lld:pubmed |
| pubmed-article:11884607 | pubmed:author | pubmed-author:MuraokaRebecc... | lld:pubmed |
| pubmed-article:11884607 | pubmed:author | pubmed-author:LenferinkAnne... | lld:pubmed |
| pubmed-article:11884607 | pubmed:author | pubmed-author:LawBrianB | lld:pubmed |
| pubmed-article:11884607 | pubmed:author | pubmed-author:RoebuckL... | lld:pubmed |
| pubmed-article:11884607 | pubmed:author | pubmed-author:ArteagaCarlos... | lld:pubmed |
