Source:http://linkedlifedata.com/resource/pubmed/id/20581865
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
36
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| pubmed:dateCreated |
2010-9-9
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| pubmed:abstractText |
Centrosome amplification (CA) contributes to carcinogenesis by generating aneuploidy. Elevated frequencies of CA in most benign breast lesions and primary tumors suggest a causative role for CA in breast cancers. Clearly, identifying which and how altered signal transduction pathways contribute to CA is crucial to breast cancer control. Although a causative and cooperative role for c-Myc and Ras in mammary tumorigenesis is well documented, their ability to generate CA during mammary tumor initiation remains unexplored. To answer that question, K-Ras(G12D) and c-Myc were induced in mouse mammary glands. Although CA was observed in mammary tumors initiated by c-Myc or K-Ras(G12D), it was detected only in premalignant mammary lesions expressing K-Ras(G12D). CA, both in vivo and in vitro, was associated with increased expression of the centrosome-regulatory proteins, cyclin D1 and Nek2. Abolishing the expression of cyclin D1, Cdk4 or Nek2 in MCF10A human mammary epithelial cells expressing H-Ras(G12V) abrogated Ras-induced CA, whereas silencing cyclin E1 or B2 had no effect. Thus, we conclude that CA precedes mammary tumorigenesis, and interfering with centrosome-regulatory targets suppresses CA.
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| pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/K01CA104079,
http://linkedlifedata.com/resource/pubmed/grant/P01CA097189,
http://linkedlifedata.com/resource/pubmed/grant/R01 CA151521-01,
http://linkedlifedata.com/resource/pubmed/grant/R01 CA151521-02,
http://linkedlifedata.com/resource/pubmed/grant/R01CA121275,
http://linkedlifedata.com/resource/pubmed/grant/R01CA85619,
http://linkedlifedata.com/resource/pubmed/grant/R01CA98371,
http://linkedlifedata.com/resource/pubmed/grant/R01HD042619,
http://linkedlifedata.com/resource/pubmed/grant/R01HD047470,
http://linkedlifedata.com/resource/pubmed/grant/U01 CA105490
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
1476-5594
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:day |
9
|
| pubmed:volume |
29
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
5103-12
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| pubmed:dateRevised |
2011-3-4
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| pubmed:meshHeading |
pubmed-meshheading:20581865-Animals,
pubmed-meshheading:20581865-Apoptosis,
pubmed-meshheading:20581865-Cell Proliferation,
pubmed-meshheading:20581865-Cell Transformation, Neoplastic,
pubmed-meshheading:20581865-Cells, Cultured,
pubmed-meshheading:20581865-Centrosome,
pubmed-meshheading:20581865-Cyclin D1,
pubmed-meshheading:20581865-Cyclin-Dependent Kinase 4,
pubmed-meshheading:20581865-Epithelial Cells,
pubmed-meshheading:20581865-Female,
pubmed-meshheading:20581865-Fibrocystic Breast Disease,
pubmed-meshheading:20581865-Genes, ras,
pubmed-meshheading:20581865-Humans,
pubmed-meshheading:20581865-Mammary Glands, Animal,
pubmed-meshheading:20581865-Mice,
pubmed-meshheading:20581865-Mice, Transgenic,
pubmed-meshheading:20581865-Protein-Serine-Threonine Kinases,
pubmed-meshheading:20581865-Signal Transduction
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| pubmed:year |
2010
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| pubmed:articleTitle |
The Ras oncogene signals centrosome amplification in mammary epithelial cells through cyclin D1/Cdk4 and Nek2.
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| pubmed:affiliation |
Department of Radiation Oncology, Emory University School of Medicine, and Emory Winship Cancer Institute, Atlanta, GA 30322, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|