Constitutive expression and regulation of collagenase-3 in human breast cancer cells.
Matrix metalloproteinases (MMPs) are a family of secreted or transmembrane proteins that have been implicated in multiple physiological and pathological processes related to extracellular matrix turnover. Recent evidence strongly suggests a role for collagenase-3 (MMP-13) in tumor metastasis and invasion. We report here that collagenase-3 is constitutively expressed in the breast cancer cell line MDA-MB231 (MDA) and outline the molecular mechanism regulating its expression. Functional analysis of the collagenase-3 promoter showed that both the activator protein-1 (AP-1) site and the runt domain (RD) binding site were required for maximal constitutive expression of collagenase-3 in MDA cells. Determination of factors binding to those sites by Northern analysis and transient transfections identified the requirement of Fra-1, c-Jun, and Cbfa1 for basal collagenase-3 promoter activity in MDA cells.
Selvamurugan
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Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, Missouri 63104, USA. selvamur@slu.edu
Partridge
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NC
D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017364:Collagenases / Q000235:genetics* / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D016758:Genes, jun / Q000235:genetics; D006801:Humans; D053509:Matrix Metalloproteinase 13; D009363:Neoplasm Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000075142:RUNX1 Translocation Partner 1 Protein; D020218:Response Elements / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099169:Fos-Related Antigen 1
D017364:Collagenases; D050659:Core Binding Factor Alpha 1 Subunit; D004268:DNA-Binding Proteins; D053509:Matrix Metalloproteinase 13; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D000075142:RUNX1 Translocation Partner 1 Protein; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000099169:Fos-Related Antigen 1; C082222:RUNX1T1 protein, human; C507079:MMP13 protein, human