Evaluation of Roles of Interferongamma Regulated Genes in Estradiol Inhibition of Androgen-Independent Prostate Cancer
Abstract
Prostate cancer 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 prostate cancer in animal models. Among the genes up-regulated by E2 are interferon gamma (IFNgamma)-regulated genes, which may be involved in direct growth inhibition by estrogen. 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 IFNgamma in vitro. The objectives of this proposal are to examine effects of E2 and IFNgamma on CaP growth and apoptosis, and expression of IPNgamma-regulated genes in hormone-independent CaP cells in vitro. We have treated four CaP cell lines, DU145, PC-3, LNCaP, and C4-2E, with E2 and IFNgamma, but to date none of the cell lines evaluated has exhibited properties similar to those of LuCaP 35V in vivo. DU145 cells were inhibited only by a high concentration of E2, while LNCaP and C4-2B were stimulated, and PC-3 were not affected. IFNgamma did not affect proliferation of any of these cells. The expression changes in IFNgamma-regulated genes subsequent to E2 treatment also did not resemble those detected in E2-treated LuCaP 35V in vivo. In the no-cost extension of this grant we will examine LAPC-4 cells, which express a wild-type androgen receptor.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA447538
Entities
People
- Eva Corey
Organizations
- University of Washington