PGR (progesterone receptor)

The progesterone receptor gene PGR is located on 11q22.1. The functional gene has 8 exons and 7 introns; the transcript is translated into 933 residues. The protein occurs as three isoforms viz. PR-A; PR-B; PR-C and 11 splice variants. PR-A and PR-B are structurally similar. The function of the splice variants is unclear, although some variants might be translated and others differentially expressed. The nuclear receptor PR isoforms are ubiquitously and uniformly expressed in target tissues. They may show differential expression in neoplasia with progressive changes. In the conventional pathway, PR undergoes conformational changes upon ligand interaction, translocates into the nucleus and binds PREs of responsive genes. PR can also function by non-genomic mode. It can activate the extra nuclear receptors, mPRs and PGRMC1 to influence cell proliferation and invasion via non-canonically routes. Both genomic and non-genomic modes of signaling may determine the relevance and the validity of PR in the progression, prognosis and management of breast cancer. The PR engages several systems, among them are PI3K/Akt/ MAPK and Wnt to influence cell adhesion, proliferation and apoptosis. The ER/PR axis is crucial in breast cancer, where the physiological outcome would be affected by the differential signaling initiated by the canonical andthe non-canonical receptors. The crosstalk between the ER/PR axis and the growth factor/PI3K/Akt/mTOR system is also highly relevant. PGR mutations and polymor