Adjuvant Action of Hepatocyte Growth Factor in Vitamin D Therapy of Androgen-Unresponsive Prostate Cancer
Abstract
This research is aimed at discovering new therapies for advanced prostate cancer and developing in preclinical models a treatment for androgen-independent prostate cancer that bolsters vitamin D's antitumor actions. We are examining separate and combined growth-regulatory effects of growth factors and hormones with vitamin D. While we are focused on paradoxical growth-inhibitory actions of hepatocyte growth factor (HGF), we are also seeking agents that act similarly with vitamin D. The initial year concentrated on developing information and model systems for characterizing androgen modulation of HGF's actions and interactions with vitamin D vis-a'- vis growth inhibition and cell-cycle regulation in sublines transformed with stable or inducible androgen-receptor activity. From this work we hope to identify which, if any, androgenic modulating influences are mediated by signaling events related to HGF's activation of MET, the HGF receptor. In seeking agents similar to HGF'S, we discovered methoxyestradiol, a normal estrogen metabolite that also exerts late cell-cycle inhibitory actions. Because it is naturally occurring, readily synthesized, and reported to lack the angiogenic and other pleomorphic effects that characterize HGF activity in normal tissues, methoxyestradiol could provide a cancer-cell-specific adjuvant to vitamin D therapy of prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADB256645
Entities
People
- Bernard A. Roos
Organizations
- University of Miami