Our study showed that high circulating estrogens and estrogen receptor beta (ERβ) may be implicated in prostate cancer (PCa) progression, and had higher expression level in African American (AA) than Caucasian American (CA) men. However, the underlying mechanisms remain elusive. The objective of this study was to investigate the signaling cross-talk between ERβ; and AR in vitro and in vivo levels. Prostate cancer cells; LNCaP, C4-2B and PC3 were treated with different concentrations and at different time points with 17β-Estradiol (E2) and 5α-dihydrotestosterone (DHT) and examined for cell proliferation by WST assay, promoter activity by luciferase assay, DNA-protein interaction by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay. After E2 or DHT treatment, the translocation of ERβ; and AR in PCa cells was also examined using fluorescence microscope.

Our results show that ERβ; was stimulated by treatment of cells with 10nM DHT and AR was also induced by treating PCa cells with10nM E2. These results were confirmed by promoter activity of truncated psPSA-luc in either PCa cell lines or Cos-7 cells. The predesigned Androgen Response Element (ARE) was bound to the protein's receptor after E2 induction. ChIP experiment corroborated the cross-talk between AR and ERβ; after treating C4-2B cells with 10nM E2 for 30 min up to 1.5 hr. Immunofluorescence depicted colocalization of AR and ERβ; in the nucleus after 30 min from E2 treatment. To our knowledge, this is the first report demonstrating crosstalk between ERβ; and AR signaling in PCa in response to E2 treatment. Our results implicate potential therapeutic application by targeting AR and ERβ; in castration-resistant PCa (CRPC).

Citation Format: Zakaria Y. Abd Elmageed, Hogyoung Kim, Raju Thomas, Krishnarao Moparty, Asim B. Abdel-Mageed. Estradiol-ERβ signaling axis in disparity of prostate cancer in African American men. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C72. doi:10.1158/1538-7755.DISP13-C72

©2014 American Association for Cancer Research.
2014