Source:http://linkedlifedata.com/resource/pubmed/id/10738245
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2000-4-20
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pubmed:abstractText |
bcl-2 expression is often associated with poor prognosis in several types of tumors; however, the role of this molecule in breast cancer is still controversial. We found earlier that over-expression of bcl-2 in a human breast-cancer cell line (MCF7(ADR)) enhances its tumorigenicity and metastatic potential by inducing metastasis-associated properties such as increased secretion of the matrix metalloproteinase-9 (mmp-9). In the present study, we investigated the effect of bcl-2 over-expression on the activity of the transcription factor NF-kappaB, an important regulator of genes involved in tumor progression and invasion. Transient transfection experiments indicate that over-expression of bcl-2 in the MCF7(ADR) cell line, enhances NF-kappaB-dependent transcriptional activity. Mobility-shift analysis revealed an increase of NF-kappaB DNA-binding in bcl-2-over-expressing clones that correlated with lower levels of the NF-kappaB cytoplasmic inhibitor IkappaBalpha. Moreover, point mutations of 2 highly conserved residues within the BH1 and BH2 domains that abrogate the interaction of bcl-2 with bax, or deletion of the N-terminal BH4 domain, completely eliminate the ability of this molecule to up-regulate NF-kappaB-dependent transactivation. Since mmp-9 is a NF-kappaB-regulated gene, we also investigated whether bcl-2 over-expression up-regulated mmp-9 transcription. We found that induction of mmp-9 mRNA correlates with the activation of an mmp-9-promoter-reporter-gene construct in transient transfection assay, and a mutation of the (-600)mmp-9-NF-kappaB binding element abolishes this effect. The overall data indicate that bcl-2-mediated regulation of NF-kappaB-transcription-factor activity may represent an important mechanism for the promotion of malignant behavior in MCF-7(ADR) 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/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0020-7136
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2000 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
86
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
188-96
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pubmed:dateRevised |
2007-7-24
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pubmed:meshHeading |
pubmed-meshheading:10738245-Binding Sites,
pubmed-meshheading:10738245-Breast Neoplasms,
pubmed-meshheading:10738245-DNA,
pubmed-meshheading:10738245-DNA-Binding Proteins,
pubmed-meshheading:10738245-Gene Expression,
pubmed-meshheading:10738245-Genes, bcl-2,
pubmed-meshheading:10738245-Humans,
pubmed-meshheading:10738245-I-kappa B Proteins,
pubmed-meshheading:10738245-Matrix Metalloproteinase 9,
pubmed-meshheading:10738245-NF-kappa B,
pubmed-meshheading:10738245-Point Mutation,
pubmed-meshheading:10738245-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:10738245-RNA, Messenger,
pubmed-meshheading:10738245-Transcription, Genetic,
pubmed-meshheading:10738245-Transfection,
pubmed-meshheading:10738245-Tumor Cells, Cultured
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pubmed:year |
2000
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pubmed:articleTitle |
bcl-2 over-expression enhances NF-kappaB activity and induces mmp-9 transcription in human MCF7(ADR) breast-cancer cells.
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pubmed:affiliation |
Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Rome, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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