Source:http://linkedlifedata.com/resource/pubmed/id/17914096
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2007-10-4
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pubmed:abstractText |
Jab1 is a co-activator of activating protein-1 (AP-1) transcription factor and the fifth subunit of the constitutive photomorphogenesis 9 (COP9) signalosome, which has been shown to mediate nuclear exportation and ubiquitin-dependent degradation of the tumor suppressor p27(Kip1). Jab1 is overexpressed in several types of human cancer. However, de-regulation of Jab1 gene expression in cancer cells is largely unclear. In this study, we reported that expression of Jab1 was stimulated by HER-2/neu oncogene via transcriptional activation. Promoter deletion and mutation analysis indicated that HER-2/neu stimulated Jab1 via the T cell factor (TCF) binding site located at the -380/-368 region of the human Jab1 promoter. DNA affinity precipitation assay and chromatin immunoprecipitation assay verified that binding of beta-catenin and TCF-4 to this consensus site was increased by HER-2/neu. In addition, dominant-negative mutant of TCF significantly attenuated the stimulatory effect of HER-2/neu. We also demonstrated that HER-2/neu increased beta-catenin/TCF-mediated Jab1 expression via the AKT signaling pathway because chemical inhibitor or dominant-negative mutant of AKT effectively attenuated the stimulatory action of HER-2/neu. IGF-I, which is a well-known AKT activator, also up-regulated the expression of Jab1 in NIH/3T3 and MCF-7 cells. Knockdown of Jab1 by small interfering RNA (siRNA) preferentially inhibited proliferation of HER-2/neu-overexpressing breast cancer cells. Taken together, our results suggest that HER-2/neu transcriptionally activates Jab1 expression to promote proliferation of breast cancer cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/COPS5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein v-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/TCF Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1351-0088
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
655-67
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17914096-Animals,
pubmed-meshheading:17914096-Binding Sites,
pubmed-meshheading:17914096-Breast Neoplasms,
pubmed-meshheading:17914096-Cell Proliferation,
pubmed-meshheading:17914096-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17914096-Humans,
pubmed-meshheading:17914096-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:17914096-Mice,
pubmed-meshheading:17914096-NIH 3T3 Cells,
pubmed-meshheading:17914096-Oncogene Protein v-akt,
pubmed-meshheading:17914096-Peptide Hydrolases,
pubmed-meshheading:17914096-Promoter Regions, Genetic,
pubmed-meshheading:17914096-RNA, Small Interfering,
pubmed-meshheading:17914096-Receptor, erbB-2,
pubmed-meshheading:17914096-Signal Transduction,
pubmed-meshheading:17914096-TCF Transcription Factors,
pubmed-meshheading:17914096-Transcriptional Activation,
pubmed-meshheading:17914096-Transfection,
pubmed-meshheading:17914096-Tumor Cells, Cultured,
pubmed-meshheading:17914096-beta Catenin
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pubmed:year |
2007
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pubmed:articleTitle |
HER-2/neu transcriptionally activates Jab1 expression via the AKT/beta-catenin pathway in breast cancer cells.
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pubmed:affiliation |
College of Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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