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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
28
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pubmed:dateCreated |
2005-6-30
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pubmed:abstractText |
An emerging paradigm holds that loss of negative signalling to receptor tyrosine kinases (RTKs) is permissive for their oncogenic activity. Herein, we have addressed tumor suppression by RALT/MIG-6, a transcriptionally controlled feedback inhibitor of ErbB RTKs, in breast cancer cells. Knockdown of RALT expression by RNAi enhanced the EGF-dependent proliferation of normal breast epithelial cells, indicating that loss of RALT signalling in breast epithelium may represent an advantageous condition during ErbB-driven tumorigenesis. Although mutational inactivation of the RALT gene was not detected in human breast carcinomas, RALT mRNA and protein expression was strongly and selectively reduced in ERBB2-amplified breast cancer cell lines. Reconstitution of RALT expression in ERBB2-amplified SKBr-3 and BT474 cells inhibited ErbB-2-dependent mitogenic signalling and counteracted the ability of ErbB ligands to promote resistance to the ErbB-2-targeting drug Herceptin. Thus, loss of RALT expression cooperates with ERBB2 gene amplification to drive full oncogenic signalling by the ErbB-2 receptor. Moreover, loss of RALT signalling may adversely affect tumor responses to ErbB-2-targeting agents.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, Humanized,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/MIG-6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/trastuzumab
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4540-8
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15856022-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:15856022-Antibodies, Monoclonal,
pubmed-meshheading:15856022-Antibodies, Monoclonal, Humanized,
pubmed-meshheading:15856022-Antineoplastic Agents,
pubmed-meshheading:15856022-Breast Neoplasms,
pubmed-meshheading:15856022-Carcinoma,
pubmed-meshheading:15856022-Cell Line, Tumor,
pubmed-meshheading:15856022-DNA Mutational Analysis,
pubmed-meshheading:15856022-Drug Resistance, Neoplasm,
pubmed-meshheading:15856022-Epidermal Growth Factor,
pubmed-meshheading:15856022-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:15856022-Female,
pubmed-meshheading:15856022-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15856022-Humans,
pubmed-meshheading:15856022-Loss of Heterozygosity,
pubmed-meshheading:15856022-Receptor, erbB-2,
pubmed-meshheading:15856022-Signal Transduction,
pubmed-meshheading:15856022-Tumor Suppressor Proteins
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pubmed:year |
2005
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pubmed:articleTitle |
Loss of RALT/MIG-6 expression in ERBB2-amplified breast carcinomas enhances ErbB-2 oncogenic potency and favors resistance to Herceptin.
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pubmed:affiliation |
Laboratory of Immunology, Regina Elena Cancer Institute, via Delle Messi d'Oro, 156/158, 00158, Rome, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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