Accession Number:

ADA411303

Title:

Novel Breast Tumor Metalloproteinase Inhibitor

Descriptive Note:

Final rept. 15 Sep 1999-14 Sep 2002

Corporate Author:

CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB

Personal Author(s):

Report Date:

2002-10-01

Pagination or Media Count:

13.0

Abstract:

Matrix Metalloproteinases MMP are a family of enzymes that collectively degrade components of the extracellular matrix ECM. A family of proteins called TIMP Tissue Inhibitor of Metalloproteinase are considered the primary protein inhibitors that modulate MMP activity. However, other polypeptides have been shown to inhibit MMP in vitro. MMP have been implicated in tumor growth and metastasis in general and breast tumors in specific. In the breast, MMP may also be involved in tumor fibrosis because the synthesis and -degradation of ECM is no longer in balance. Understanding factors that modulate MMP activity is important to understand breast tumor biology. Previously, we identified a non-TIMP inhibitor that was the C-terminal region of Procollagen C-terminal Proteinase Enhancer. This novel inhibitor was designated CT-PCPE. Intact PCPE has no metalloproteinase inhibitor activity. Activity is revealed by proteolytic processing of the parent PCPE. We have observed CT-PCPE and other small non-TIMP inhibitors in the medium conditioned by an aggressive breast tumor cell line. To investigate the role of CT-PCPE in breast tumors, PCPE and CT-PCPE have been expressed for the purpose of characterization of inhibitor activity and CT-PCPE production. Additionally, another putative non-TIMP inhibitor has been identified in breast tumor cell conditioned medium.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE