Rbf/E2F1 control growth and endoreplication via steroid-independent Ecdysone Receptor signalling in < i > Drosophila < /i > prostate-like secondary cells

by Aashika Sekar, Aaron Leiblich, S. Mark Wainwright, Cl áudia C. Mendes, Dhruv Sarma, Josephine E. E. U. Hellberg, Carina Gandy, Deborah C. I. Goberdhan, Freddie C. Hamdy, Clive Wilson In prostate cancer, loss of the tumour suppressor gene,Retinoblastoma (Rb), and consequent activation of transcription factor E2F1 typically occurs at a late-stage of tumour progression. It appears to regulate a switch to an androgen-independent form of cancer, castration-resistant prostate cancer (CRPC), which frequently still requires androgen receptor (AR) signalling. We have previously shown that upon mating, binucleate secondary cells (SCs) of theDrosophila melanogaster male accessory gland (AG), which share some similarities with prostate epithelial cells, switch their growth regulation from a steroid-dependent to a steroid-independent form of Ecdysone Receptor (EcR) control. This physiological change induces genome endoreplication and allows SCs to rapidly replenish their secretory compartments, even when ecdysone levels are low because the male has not previously been exposed to females. Here, we test whether theDrosophila Rb homologue, Rbf, and E2F1 regulate this switch. Surprisingly, we find that excess Rbf activity reversibly suppresses binucleation in adult SCs. We also demonstrate that Rbf, E2F1 and the cell cycle regulators, Cyclin D (CycD) and Cyclin E (CycE), are key regulators of mating-dependent SC endoreplication, as well as SC growth in both virgin and mated males. Import...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research