Novel Breast Tumor Metalloproteinase Inhibitor
Abstract
Matrix Metalloproteinases (MMP) are a family of enzymes that degrade the extracellular matrix. Modulation of MMP activity may attenuate the invasiveness of some tumors. MMP activity may also be involved in breast tumor fibrosis because the balance of connective tissue synthesis and degradation is lost. Understanding factors that modulate MMP activity are therefore important to understanding breast tumor biology. We have identified a metalloproteinase inhibitor associated with an invasive breast tumor cell line. The inhibitor was determined not to be a TIMP (Tissue Inhibitor of Metalloproteinase) which are currently the only known metalloproteinase inhibitors. The novel inhibitor (CT-PCPE) was found to be the C-terminal portion of a protein known as Procollagen C-terminal Proteinase Enhancer (PCPE). Intact PCPE has no inhibitor activity. Activity was revealed only by proteolytic processing of the parent PCPE molecule. To investigate CT-PCPE in breast tumors, a plasmid containing the region of CT-PCPE homologous to TIMP was constructed. The structure of expressed CT-PCPE will be compared to TIMP in an effort to better understand CT-PCPE inhibition of MMP. In addition, a proteinase has been observed in the conditioned medium of tumor cell lines that process PCPE to CT-PCPE. Evidence suggests that this may be the proteinase responsible for PCPE processing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA388213
Entities
People
- Michael J. Banda
Organizations
- University of California, Berkeley