Signal Transduction Pathway in Maspin-Induced Tumor Suppression of Prostate Cancer
Annual rept. 1 Sep 1999-28 Feb 2001
UNIVERSITY OF CENTRAL FLORIDA ORLANDO
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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 hepsins role in cancer. Our findings may lead to the development of diagnostics or drugs leads.
- Anatomy and Physiology
- Medicine and Medical Research