The Role of a Novel Protease NES1 in Breast Cancer
Abstract
NES1 gene is expressed in normal mammary epithelial (MECs) and prostate cells, but its mRNA and protein expression is dramatically decreased in most established breast, prostate and cervical cancer cell lines even though no major deletion or rearrangements in NESl gene are found. Inspite of high homology of NESl polypeptide to known serine proteases, it lacks any detectable protease activity. This is probably due to the unusual amino terminus of NESl that contains LDPEAY instead of IVGG (present in most active serine proteases). IVGG sequence is required for salt bridge formation. Transfection of NESl cDNA into NESl-negative breast cancer cell line suppressed the anchorage-independent growth and tumor formation in nude mice. NESl gene is localized on to chromosome l9ql3.3. Cloning of NESl promoter and analyses of its activity showed that most tumor cell lines were able to support full or partial transcription from NESl promoter. We show that hypermethylation of NESl gene on exon 3 is responsible for lack of NESl expression in tumor cell lines and in primary breast tumors. In summary, we accomplished most of the tasks in Aim I, II and III. In addition, we defined the mechanism of loss of NESl expression in tumor cells. Future studies should focus on analyses to evaluate NESl expression/hypermethylation as potential marker for diagnosis and/or prognosis of breast and other cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2001
- Accession Number
- ADA391320
Entities
People
- Vimla Band