School of Electrical and Electronic Engineering, University of Newcastle Upon Tyne, Newcastle Upon Tyne UK and the Institute for Molecular Medicine, Huntington Beach CA, USA; firstname.lastname@example.org; email@example.com
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 and the 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 polymorphism are infrequent in cancers. The polymorphic PROGINS has been linked, not indisputably, with cancer risk. Many SNPs have been identified, mostly inconsequential ones. Some may be related to breast, endometrial and colorectal cancer risk. PR produces good clinical outcome in breast cancer independently of ER. It displays greater correlation than ER with disease progression and prognosis. It may be differentially expressed in benign prostatic hyperplasia and progressive cancer. The expression may reflect androgen-insensitivity. PROGINS is said to increase ovarian cancer risk, but, paradoxically, reduce breast cancer risk. The use of progesterone antagonists or agonists has been advocated. PRs can act as activators or repressors of transcription, necessitating the identification of the functional PR\/ER isoforms. Some new progestins, employed in HRT, have been claimed to prevent certain forms of cancer.
PGR (progesterone receptor)
Atlas Genet Cytogenet Oncol Haematol. 2017-02-01
Online version: http://atlasgeneticsoncology.org/gene/41700/pgr-(progesterone-receptor)