Signal Transduction Pathway in Maspin-Induced Tumor Suppression of Prostate Cancer
Abstract
The purpose was to identify a maspin receptor. Prostasin and hepsin serine proteases were examined as candidates. Prostasin down-regulation observed in high-grade prostate cancer eliminated this protease as a candidate. Prostasin expression is absent in highly invasive DU-145 and PC-3 cells, while expressed in normal human prostate epithelial cells and the non-invasive LNCaP cells. A forced re-expression of prostasin in DU-145 and Pc-3 cells reduced the invasiveness by 68% and 42%, respectively, while showing no effect on cell proliferation. The anti-invasion property was associated with cellular prostasin, which exists on cell membrane as an active protease via a GPI-anchor. In DU-145 and PC-3 cells expressing recombinant prostasin, a protein band at 120-130 kDa range in SDS-PAGE was found to be reduced in tyrosine phosphorylation while a reduction of protein kinase C alpha expression was also observed. These cellular protein changes elicited by prostasin expression provide leads for investigation of prostasin anti-invasion signal transduction. We demonstrated an up-regulation of hepsin in prostate cancer and are in pursuit of maspin-hepsin interaction by yeast genetics. Drosophila genetics will also be employed to investigate hepsin's role in cancer. Our findings may lead to the development of diagnostics or drugs leads.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2001
- Accession Number
- ADA394018
Entities
People
- Karl X. Chai
Organizations
- University of Central Florida