Role of a Mitochondrial Progesterone Receptor in the Growth of Breast Epithelial Cells

摘要

This proposal proves a new molecular mechanism whereby progesterone via a mitochondrial receptor, named PR-M, influences the growth of breast cancer cells by enhancing cellular respiration. For this purpose we developed an RNAi assay to silence expression of PR-M in T47D breast cancer cells. We have demonstrated with this assay a decrease in PR-M transcript levels by qRT- PCR and a decrease in protein levels with western blot analysis. Functionally, we then demonstrated a decrease in progesterone/progestin induced mitochondrial membrane potential with silencing of PR-M expression. We then sought to determine the influence of PR-M silencing on the metabolomic pathway of these cells. These studies are still ongoing but initially suggest an increase in lipid catabolism with increased levels of acylcarnitines. These results suggest that progesterone increases cellular energy production by influencing fatty acid oxidation via a unique mitochondrial progesterone receptor. This provides a new mechanism whereby progesterone influences the growth and survival of breast cancer cells.