Progesterone receptors act as sensors for mitogenic protein kinases in breast cancer models

Progesterone receptors (PR), members of the nuclear receptor superfamily, function as ligand-activated transcription factors and initiators of c-Src kinase and mitogen-activated protein kinase signaling. Bidirectional cross-talk between PR and mitogenic protein kinases results in changes in PR post-translational modification, leading to alterations in PR transcriptional activity and promoter selectivity. PR-induced rapid activation of cytoplasmic protein kinases insures precise regulatory input to downstream cellular processes that are dependent upon nuclear PR, such as cell-cycle progression, and pro-survival signaling. Here, we review interactions between PR and mitogenic protein kinases and discuss the consequences of specific post-translational modifications on PR action in breast cancer cell-line models.