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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
2005-5-9
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pubmed:abstractText |
HER-2 is constitutively activated and overexpressed in many cancers, and its inhibition in colon cancer cells diminishes tumorigenicity and induces apoptosis. Little is known about the regulation of HER-2 signaling in colon cancer cells. Integrin alpha5/beta1 expression is frequently lost in colorectal cancer cells compared with normal intestinal epithelium, and colon cancer cells lacking integrin alpha5/beta1 expression utilize HER-2 signaling for proliferation and tumorigenicity. Re-expression of integrin alpha5/beta1 in colon cancer cells abrogated their tumorigenicity, but how this occurs is not well known. Stable expression of integrin alpha5/beta1 in colon cancer cells with little or no detectable integrin alpha5/beta1 protein expression resulted in the post-transcriptional down-regulation of HER-2 protein. Integrin alpha5/beta1 was found to interact with HER-2, and the cytoplasmic domain of integrin alpha5/beta1 was sufficient to mediate HER-2 down-regulation. Integrin alpha5/beta1-mediated down-regulation of HER-2 was the result of increased lysosomal targeting. The inhibition of HER-2 signaling represents a potential mechanism by which integrin alpha5/beta1 exerts its tumor suppressor-like activity in colon cancer cells. These results also suggest that a novel function for integrin alpha5/beta1 is the control of HER-2 expression.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19027-35
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15757908-Agar,
pubmed-meshheading:15757908-Biotinylation,
pubmed-meshheading:15757908-Blotting, Northern,
pubmed-meshheading:15757908-Caco-2 Cells,
pubmed-meshheading:15757908-Cell Line, Tumor,
pubmed-meshheading:15757908-Cell Membrane,
pubmed-meshheading:15757908-Cell Proliferation,
pubmed-meshheading:15757908-Colonic Neoplasms,
pubmed-meshheading:15757908-Cytoplasm,
pubmed-meshheading:15757908-Down-Regulation,
pubmed-meshheading:15757908-Extracellular Matrix,
pubmed-meshheading:15757908-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15757908-Green Fluorescent Proteins,
pubmed-meshheading:15757908-Humans,
pubmed-meshheading:15757908-Immunoblotting,
pubmed-meshheading:15757908-Immunoprecipitation,
pubmed-meshheading:15757908-Integrin alpha5beta1,
pubmed-meshheading:15757908-Lysosomes,
pubmed-meshheading:15757908-Mutagenesis, Site-Directed,
pubmed-meshheading:15757908-Phosphorylation,
pubmed-meshheading:15757908-Protein Structure, Tertiary,
pubmed-meshheading:15757908-RNA, Messenger,
pubmed-meshheading:15757908-RNA Processing, Post-Transcriptional,
pubmed-meshheading:15757908-Receptor, erbB-2,
pubmed-meshheading:15757908-Signal Transduction,
pubmed-meshheading:15757908-Time Factors,
pubmed-meshheading:15757908-Transcription, Genetic,
pubmed-meshheading:15757908-Transfection
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pubmed:year |
2005
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pubmed:articleTitle |
Integrin alpha5/beta1 expression mediates HER-2 down-regulation in colon cancer cells.
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pubmed:affiliation |
Department of Medicine, Salt Lake City Veterans Administration Health Care System and Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA.
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pubmed:publicationType |
Journal Article
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