Abstract 4361: A systematic study of the impact of estrogens and selective estrogen receptor modulators on prostate cancer cell proliferation

Abstract

Abstract The estrogen receptors ERα and ERβ are expressed in prostate cancer (PCa) cells and are believed to act as an oncogene and a tumor suppressor, respectively, and thus to be attractive therapeutic targets. Indeed, compounds modulating the activity of these receptors already exist and are currently used to treat ERα-positive breast tumors. However, there is a lot of discrepancies regarding the efficacy of anti-estrogen treatments for the management of PCa. Several factors explain these discrepancies, including unspecific antibodies against ERβ, lack of proper estrogenic positive controls, and usage of estrogens and anti-estrogens molecules at high dosages were off-target effects are observed. Our objective was to conduct a systematic study on the impact of estrogenic and anti-estrogenic ligands on PCa cell proliferation and survival. After optimization of our cellular assay using the human breast cancer cell line MCF7, we used five of the most commonly studied human PCa cell models, namely LNCaP, 22Rv1, LAPC4, DU145, and PC3 cells. These cells were treated with nine estrogenic/anti-estrogenic compounds, including five selective estrogen receptor modulators (SERMs), with and without co-treatment with androgens for androgen receptor (AR)-positive cells. In both AR-positive and AR-negative cells, we observed no significant modulation of proliferation following modulation of ERs activity. Using both RNA-seq and Western Blots, ERs expression was mostly undetectable in these models. Our study indicate that commonly used PCa models in vitro are not appropriate models to study the estrogen signaling pathway in PCa. Yet, expression data from PCa tissues indicate a significant expression of both receptors, and indicate that usage of new PCa models or of in vivo models are required to properly study drug repurposing of anti-estrogens and SERMs for PCa treatment. Citation Format: Camille Lafront, Lucas Germain, Cindy Weidmann, Etienne Audet-Walsh. A systematic study of the impact of estrogens and selective estrogen receptor modulators on prostate cancer cell proliferation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4361.