A Novel Mechanism of Androgen Receptor Action
Annual rept. 15 Dec 2004-14 Dec 2005
OREGON HEALTH AND SCIENCES UNIV PORTLAND
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This project had as its original goal the elucidation of a novel mode of action of the androgen receptor that may be of importance in the initiation and progression of prostate cancer. Specifically, the authors had determined that the androgen receptor controls the expression of the cell-surface receptor for the hormone IGF-1 at the level of translation of the IGF-1 receptor mRNA in an androgen-independent fashion. In the course of studies in the first year of funding, they serendipitously found another factor that also regulates IGF-1 receptor expression and action, and that also inhibits the expression and action of the EGFRerbBHER family of receptor tyrosine kinases. This protein, an alternative product of the HER2 proto-oncogene termed herstatin, has the potential ability to function as a novel bifunctional inhibitor of both the EGF and IGF signaling systems, which are themselves independently implicated in prostate cancer initiation and progression. The authors propose to re-orient their studies to focus on this potential anti-tumor factor in prostate cancer cells and to determine its potential therapeutic utility. These studies are conceptually in line with their original proposal in that they address a novel mechanism of control of IGF-1 receptor expression and action and its role in prostate cancer tumorigenesis and metastasis.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research