Progesterone receptor effects on cell morphology and EMT associated genes in breast cancer cells

Epithelial-mesenchymal transition (EMT) is a key biological process associated with invasion and metastasis in breast cancer. Our recent data suggests that introduction of progesterone receptor (PR) into PR-negative, ER-positive T47DY breast cancer cells can suppress EMT, supporting emerging evidence that under certain conditions steroid receptors may act as tumor suppressors. In these studies we test the effects of acute tetracycline-inducible expression of either wild-type PR (wtPR) or a mutant deficient in extra-nuclear signaling (mutPR) in T47D.C42 PR negative, ER negative breast cancer cells.  PR expression was confirmed by Western blot and quantitative RT-PCR (qPCR).  No overt changes in cell morphology were observed following induction of either wtPR or mutPR. We examined the effects of PR on expression of EMT-associated genes (vimentin, lcn2, slug) using qPCR. Vimentin expression was below the threshold of detection in the absence of PR expression and no significant differences in lcn2 or vimentin were observed following PR expression. Treatment with the synthetic progestin R5020 induced expression of slug in both wtPR and mutPR expressing cells, indicating that slug up regulation by PR is independent of its extra-nuclear signaling action. These data contrast with studies in the T47DY cell line where PR suppressed expression of these and other EMT-associated genes and resulted in cell morphology changes consistent with reversal of EMT. Experiments are ongoing to determine whether ER and PR may work together to suppress EMT and to determine whether PR can block EMT induced by various agents in normal human breast epithelial cell line models.