Signal Transduction Pathway in Maspin-induced Tumor Suppression of Prostate Cancer
Abstract
The original purpose was to identify a receptor for maspin, a serpin tumor suppressor of breast and prostate cancers. Prostasin and hepsin serine proteases were examined as candidates. Prostasin was found to be down-regulated in high-grade prostate cancers and absent in invasive prostate and breast cancer cells, in which prostasin promoter hypermethylation was found. Prostasin was shown to be an invasion suppressor, via its GPI-anchored membrane form. Prostasin is involved in epithelial sodium channel activation and is regulated by the serpin protease nexin-1 (PN-1). Other cellular protein changes elicited by prostasin expression were also observed. A new project has been initiated to investigate the mechanisms of prostasin's anti-invasion function. A second new project has been initiated to evaluate the potential of using prostasin as a metastasis suppressor of breast cancer. A new hypothesis is proposed for a potential indirect interaction between maspin and prostasin based on their individually confirmed roles in sodium transport regulation. We demonstrated an up-regulation of hepsin in prostate cancer, but no direct interaction was established between maspin and hepsin at the biochemical or cellular level. Drosophila genetics was and will continue to be employed to investigate hepsin's role in cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2002
- Accession Number
- ADB286348
Entities
People
- Karl X. Chai
Organizations
- University of Central Florida