Linked Life Data

17914096

Source:http://linkedlifedata.com/resource/pubmed/id/17914096

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-10-4
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1351-0088
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
655-67
pubmed:dateRevised
2009-11-19
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
pubmed:year
2007
pubmed:articleTitle
HER-2/neu transcriptionally activates Jab1 expression via the AKT/beta-catenin pathway in breast cancer cells.
pubmed:affiliation
College of Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't