The Role of a Novel Protese NES1 in Breast Cancer.
Abstract
The proposed studies are aimed to understand the biochemical mechanism of conversion of normal mammary epithelial cells (MECs) into tumor cells. Previously, we isolated a novel serine protease-like gene NES1 (Normal Epithelial Cell Specific-1) that is expressed in normal mammary epithelial cells but is down-regulated in most breast cancer cell lines. We now demonstrate that stable expression of NES1 in the NES1-negative MDA-MB-231 breast cancer cell line suppressed the oncogenicity as revealed by inhibition of the anchorage-independent growth and tumor formation in nude mice. Fluorescence in-situ hybridization localized the NES1 gene to chromosome 19q13.3 .3, a region that contains genes for related proteases, including the prostate specific antigen, and is rearranged in human cancers. Similar to breast cancer cell lines, prostate cancer cell lines also lacked NES1 mRNA and protein expression. Finally, we have now expressed and purified NES1 protein to homogeneity and we present data showing the protease activity of NES1 against a universal serine protease substrate (casein resourfin) and against glandular and plasma kallikrein substrates. Interestingly, the NES1 protein also exhibits protease activity against insulin like growth factor binding protein-3 (IGFBP-3). Together, these studies are aimed towards understanding the tumor suppressor role for NES1 protein in breast and other carcinomas.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA358012
Entities
People
- Vimla Band