Differential Mechanisms of Androgen Resistance
Annual summary rept. 22 Nov 2004-21 Nov 2005
MICHIGAN UNIV ANN ARBOR
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We proposed to study the mechanisms of androgen resistance by focusing on androgen receptor mutations that arise due to the selective pressures of antiandrogen treatment. In vitro we examined the mechanistic actions of bicalutamide and flutamide in transfection studies in a variety of cell lines and on different androgen responsive promoters. We have shown that flutamide exhibits agonist action in a cell specific manner. In vivo we utilized two models to test our hypothesis, xenograft models of human prostate cancer cell lines and a novel transgenic mouse model that expresses a humanized androgen receptor in the TRAMP background. We are currently assessing tumor progression in both models and sequencing AR cDNAs from tumors with different endocrine status.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology