Evaluation of Roles of Interferon Gamma Regulated Genes in Inhibition of Androgen-Independent Prostate Cancer
Final rept. 1 Feb 2004-31 Jul 2006
WASHINGTON UNIV SEATTLE
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CaP presents its greatest challenge to clinicians when it progresses to the hormone-independent state. Therapeutic methods which are effective regardless of androgen response, or even target androgen-independent CaP specifically, are of special medical and scientific interest. We have shown that estradiol E2 can inhibit growth of hormone independent CaP in vivo. Among the genes up-regulated by E2 are IFN-regulated genes. The LuCaP 35V xenograft does not grow in vitro for this reason, this exploratory proposal was design to evaluate the responses of various CaP cell lines to E2 and IFN in vitro. Our results show that E2 did not inhibit growth of 5 prostate cancer cell lines in vitro. It is possible that inhibition by E2 is not a result of direct effects of E2 on tumor cells, and that the interaction with the host environment may be critical for this inhibition. Regarding E2 regulation of expression of IFN-regulated genes, our data suggest that E2 may not activate IFN pathways directly, However our results suggest that IFN-regulated genes may play a role in the growth inhibition caused by E2 in vivo, since DU 145 cells showed similar alterations in expression of these genes following E2 treatment as LuCaP 35V, but smaller in magnitude, and DU 145 growth was weakly inhibited by high doses of E2. In conclusions, the 5 CaP cell lines available to us did not respond to E2 treatment as do LuCaP 35V in vivo. Our results indicate the possibility that the observed effects of E2 on prostate cancer xenografts in vivo might be mediated via indirect effects through interactions of CaP cells with cells of the innate immune system or other indirect effects of E2 requiring interactions with the host environment.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research