Impact from estrogen receptors on the aetiopathology of prostate carcinoma monitored in novel estrogen receptor knock out TRAMP animal models

• Applicants: Dr. Felix Bremmer; Professor Dr. Peter Burfeind; Professor Dr. Hubertus Jarry; Dr. Paul Thelen
• Subject Area: Reproductive Medicine, Urology ; Endocrinology, Diabetology, Metabolism
• Term: from 2013 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 234228309

Carcinogenesis originating from precancerous lesions in the prostate coincides with typical expression abnormalities. Pivotal aberrations occur as gain of function at the androgen receptor and develop evidently concomitant with a loss of estrogen receptor-beta expression. The aim of this project is to elucidate the coherence of these counter-acting transcription factor functions.The TRAMP mouse model qualifies best to investigate tumour biology and progression of an androgen-sensitive prostate carcinoma. In addition, crossbreeding of the individual estrogen receptor knock-out strains (ERKO = ERalpha knock out bzw. BERKO = ERbeta knock out) with the TRAMP mouse strain features meaningful new animal models for functional analyses of receptor cross talk. Furthermore, such models will yield new tumour cell lines to analyse signal transduction pathways and to evaluate synthetic or plant-derived ER subtype-selective ligands.In previous studies we demonstrated an anti-androgenic function from the estrogen receptor-beta. The project in question will investigate the potential of these receptors´ influence on carcinogenesis and will indicate novel therapeutic targets in different stages of prostate carcinoma.

• DFG Programme: Research Grants