Abstract 1715: Estrogen receptor β induces apoptosis through PUMA independent of p53 in prostate cancer cells.

Abstract Estrogen receptor β1’s (ERβ1) expression is reduced during the progression of prostate cancer. In agreement with several studies indicating a tumor suppressive effect of ERβ, we find that expression of ERβ increases apoptosis in the prostate cancer cells. Cells expressing ERβ showed an increase in apoptotic cell population by TUNEL assay and flow cytometric analysis. In addition, cells expressing ERβ showed an increase in sub G1 cell population compared to the control cells. Also, ERβ decreases the expression of anti-apoptotic factor Bcl-2 and increases the expression of the pro-apoptotic factor PUMA. Regulation of PUMA was found to be independent of p53. Although phosphorylation of AKT was decreased by ERβ expression we could not see any reduction of phosphorylated FOXO3A, a known regulator of PUMA. On the other hand total mRNA and protein of FOXO3A increased indicating a direct regulation of FOXO3A by ERβ. Using non-transfected PC3 and LNCaP cells we could observe induction of FOXO3A and PUMA as well as apoptosis in response to added 3β-adiol, DPN or 8β-VE2 indicating that the small amount of ERβ expressed in these cell lines are sufficient to induce apoptosis in response to ERβ specific ligands. Overall, our study indicates an apoptotic action of ERβ and suggests that it can be advantageous to treat prostate cancer with ERβ agonist. Citation Format: Prasenjit Dey, Jan-Ake Gustafsson, Anders M. Strom. Estrogen receptor β induces apoptosis through PUMA independent of p53 in prostate cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1715. doi:10.1158/1538-7445.AM2013-1715