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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0185117,
umls-concept:C0242957,
umls-concept:C0338204,
umls-concept:C0392756,
umls-concept:C0664336,
umls-concept:C1512505,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C2911684
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pubmed:issue |
5
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pubmed:dateCreated |
2010-6-10
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pubmed:abstractText |
Overexpression of ErbB2 is associated with poor prognosis in breast cancer. Targeting of ErbB2 is a very common therapeutic strategy in ErbB2-overexpressed breast cancer. Herceptin is the first approved and most widely used agent for ErbB2-targeting therapy in breast cancer. Even though the clinical application has been performed for more than 10 years, the exact mechanism underlying how Herceptin exhibits its effects has not been fully elucidated. In this study, we found that Herceptin could inhibit the expression of survivin in ErbB2-overexpressed cell lines. Overexpression of survivin could abrogate the inhibition of cell growth induced by Herceptin. Herceptin could reduce survivin expression at the transcriptional level. The beta-catenin/T-cell factor (TCF) pathway played a very crucial role in this cascade. We found that Herceptin could reduce tyrosine phosphorylation levels of ErbB2 and beta-catenin. Herceptin treatment induced degradation of beta-catenin protein, resulting in reduced binding affinity of beta-catenin/TCF4 to the promoter region of survivin. When we cross-mutated the TCF4 binding sites in the promoter region of survivin, the reduction of survivin promoter activity almost diminished. Taken together, we showed that Herceptin could inhibit survivin expression through the ErbB2-beta-catenin/TCF4-survivin pathway in ErbB2-overexpressed breast cancer cells. This indicates that there may be a new cascade axis from ErbB2 to survivin.
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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/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, Humanized,
http://linkedlifedata.com/resource/pubmed/chemical/BIRC5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix Leucine...,
http://linkedlifedata.com/resource/pubmed/chemical/ERBB2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/TCF4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/trastuzumab
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1349-7006
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pubmed:author |
pubmed-author:BaiJingfengJ,
pubmed-author:ChenMeiguiM,
pubmed-author:QuanLanpingL,
pubmed-author:RAOS VSV,
pubmed-author:THINJJ,
pubmed-author:UrenCC,
pubmed-author:XuNinghongN,
pubmed-author:XuNingzhiN,
pubmed-author:ZhangGuoG,
pubmed-author:ZhangWeiW,
pubmed-author:ZhuHongxiaH
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pubmed:issnType |
Electronic
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1156-62
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:20331626-Antibodies, Monoclonal,
pubmed-meshheading:20331626-Antibodies, Monoclonal, Humanized,
pubmed-meshheading:20331626-Basic Helix-Loop-Helix Leucine Zipper Transcription Factors,
pubmed-meshheading:20331626-Breast Neoplasms,
pubmed-meshheading:20331626-Cell Line, Tumor,
pubmed-meshheading:20331626-Female,
pubmed-meshheading:20331626-Humans,
pubmed-meshheading:20331626-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:20331626-Microtubule-Associated Proteins,
pubmed-meshheading:20331626-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:20331626-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:20331626-Receptor, erbB-2,
pubmed-meshheading:20331626-Transcription Factors,
pubmed-meshheading:20331626-beta Catenin
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pubmed:year |
2010
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pubmed:articleTitle |
Inhibition of ErbB2 by Herceptin reduces survivin expression via the ErbB2-beta-catenin/TCF4-survivin pathway in ErbB2-overexpressed breast cancer cells.
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pubmed:affiliation |
Laboratory of Cell and Molecular Biology, State Key Laboratory of Molecular Oncology, Beijing, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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