The Role of a Novel Protease 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 gene NES1 (Normal Epithelial Cell Specific-1), whose mRNA and protein expression was dramatically decreased in breast cancer cell lines. Homology comparison of this novel peptide showed that NES1 belongs to a family of serine proteases. Significantly, transfection-mediated reconstitution of NES1 expression in NES1-nonexpressing breast cancer cell lines suppressed the oncogenic phenotype and cell spreading on extracellular matrix. Purification of NES1 demonstrated that NES1 is synthesized as Pre-pro-NES1 and is secreted as Pro-NES1. Pro-NES1 can be activated using glandular kallikrein. Glandular kallikrein-activated NES1 cleaves IGFBP-3 as efficiently as other serine proteases. We have generated a large series of NES1 mutants that should determine the structural domains that are necessary for its protease activity as well as tumor suppressor function. Together, these studies should reveal the functional role of a novel serine protease whose expression is down-regulated in breast cancer cells. Thus, these studies should directly contribute to further our understanding of the biology of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA379295
Entities
People
- Vimla Band