A Novel Role of BCL-2 in the Regulation of Apoptosis Mediated by Remodeling and Turnover of Extracellular Matrix.
Abstract
The bcl-2 oncogene product is a potent inhibitor of apoptosis induced by a variety of stimuli. Bcl-2 is highly expressed in breast cancer and its expression is related to chemotherapy and radiation therapy resistance. Increasing evidence suggests that remodeling and turnover of extracellular matrix (ECM) play a critical role in the regulation of apoptosis in mammary epithelial cells. In the present study, our purpose is to investigate whether bcl-2 inhibition of apoptosis involves regulation of ECM-regulating gene expression using three human breast epithelial cell lines: MCFlOA, a "normal" breast epithelial cells line; TG3B, a preneoplastic cell line derived from MCFl0A; and MCF-7, a breast carcinoma cell line. Overexpression of bcl-2 up-regulates expression of tissue inhibitor of metalloproteinase- 1 (TIMP- 1), an inhibitor of matrix metalloproteinases (MMPs) in all three cell lines. Bcl-2 down-regulates expression of MMP-9 in MCFl0A cells, while MMP-9 was not detectable in TG3B and MCF-7 cells. However, phorbol ester induced MMP-9 expression was abolished by bcl-2 in all three cell lines. We are currently investigating the roles of TIMP-land MMP-9 in the regulation of apoptosis in breast epithelial cells. Our preliminary result suggests that exogenous TIMP-l partially protect MCFl0A cells against induction of apoptosis by hydrogen peroxide.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1998
- Accession Number
- ADA354104
Entities
People
- Li Gangyong
Organizations
- Wayne State University