Constitutive expression and regulation of collagenase-3 in human breast cancer cells
N Selvamurugan1, N C Partridge
1Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, Missouri 63104, USA. selvamur@slu.edu
Abstract:
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.
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