Source:http://linkedlifedata.com/resource/pubmed/id/14625284
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
2004-2-2
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| pubmed:abstractText |
The Her-2/neu oncogene is overexpressed in approximately 30% of breast and ovarian cancer cases and often indicates a poor prognosis. Therapeutic agents against Her-2/neu have been intensively sought over the past decade. Here we show that small interfering RNA (siRNA) can silence the expression of Her-2/neu in models of human breast or ovarian cancer through retrovirus-mediated transfer of an siRNA against Her-2/neu. Cells infected with retrovirus expressing anti-Her-2/neu siRNA exhibit slower proliferation, increased apoptosis, increased G0/G1 arrest, and decreased tumor growth. Changes in cell cycle-associated factors included decreased levels of phosphatidylinositol 3-kinase, pAkt, and cyclin D1 and increased levels of p27 and phosphorylated retinoblastoma protein. Knockdown of Her-2/neu expression by siRNA is also associated with increased expression of the anti-angiogenic factor thrombospondin-1 and decreased expression of the pro-angiogenic vascular endothelial growth factor, suggesting that Her-2/neu stimulates tumor growth at least in part by regulating angiogenesis. siRNA-mediated gene silencing of Her-2/neu and increasing the expression of thrombospondin-1 may be a useful therapeutic strategy for Her-2/neu-over-expressing breast or ovarian cancer.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombospondin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
6
|
| pubmed:volume |
279
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4339-45
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:14625284-Apoptosis,
pubmed-meshheading:14625284-Base Sequence,
pubmed-meshheading:14625284-Breast Neoplasms,
pubmed-meshheading:14625284-Cell Cycle Proteins,
pubmed-meshheading:14625284-Cell Division,
pubmed-meshheading:14625284-Cell Line, Tumor,
pubmed-meshheading:14625284-Female,
pubmed-meshheading:14625284-Gene Expression,
pubmed-meshheading:14625284-Gene Silencing,
pubmed-meshheading:14625284-Genes, erbB-2,
pubmed-meshheading:14625284-Genetic Vectors,
pubmed-meshheading:14625284-Humans,
pubmed-meshheading:14625284-Neovascularization, Pathologic,
pubmed-meshheading:14625284-Ovarian Neoplasms,
pubmed-meshheading:14625284-RNA, Small Interfering,
pubmed-meshheading:14625284-Retroviridae,
pubmed-meshheading:14625284-Signal Transduction,
pubmed-meshheading:14625284-Thrombospondin 1,
pubmed-meshheading:14625284-Vascular Endothelial Growth Factor A
|
| pubmed:year |
2004
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| pubmed:articleTitle |
Inhibition of breast and ovarian tumor growth through multiple signaling pathways by using retrovirus-mediated small interfering RNA against Her-2/neu gene expression.
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| pubmed:affiliation |
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4095, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|