There is accumulating evidence to suggest that progesterone plays an essential role in the regulation of growth and differentiation of mammary glands and thus may play a key role in breast cancer. The biological response to progesterone is mediated by two distinct forms of the human progesterone receptor (PR-A and PR-B forms). In most cell contexts, the B form functions as a transcriptional activator, whereas the A form functions as a transcriptional inhibitor of steroid hormones. Recently it has been demonstrated that there is differential hormone dependent regulation of the phosphorylation of the A and B forms of the receptor. Treatment of T47D breast cancer cells with progestin agonist increases the phosphorylation of Ser190 and Ser294 with different kinetics. These phosphorylation events may differentially affect the transcriptional activity of the receptor.