Progesterone Receptor Monoclonal Antibody (KMC912), eBioscience™, Invitrogen™

Description

• This KMC912 MAb reacts with human progesterone receptor (PgR, PR), a member of a superfamily of nuclear receptors that are ligand-dependent transcriptional regulators
• The human PgR exists in alpha and beta forms, 94 kDa and 120 kDa respectively
• In most human cells, the alpha and beta forms are expressed at similar levels and predominately form heterodimers
• Progestin binding to PgR causes a conformational change, allowing dissociation of bound chaperone proteins and subsequent dimerization with either PgRa or PgRb
• Following activation, dimerized PgR can directly bind to DNA through progestin response elements (PRE) leading to chromatin remodeling and subsequent downregulation or transcription of the target gene.The PgR plays a key role in controlling gene expression in breast, uterine, brain, and cardiovascular tissue during development
• The presence of the PgR in breast tissue is indicative of improved survival and a better response to endocrine therapy
• In breast and endometrial cancer progression, a predominance of either the alpha or beta form occurs, suggesting disregulation in the PgRa:PgRb ratio is an early event in cancer
• In cases of ductal carcinoma in situ and invasive ductal carcinoma, there is predominance of the alpha form while in uterine cancer a loss of either form is common
• The progesterone receptor (PR) is a member of the steroid family of nuclear receptors
• The PR mediates the physiological effects of progesterone, which plays a central role in reproductive events associated with the establishment and maintenance of pregnancy
• PR is found as a 94 kDa protein (Form A) or a 120 kDa protein (Form B) due to the use of alternative translation initiation sites
• PR-B is the transcriptionally active form and is responsible for activating genes for the maintenance of the endometrium, maintenance of pregnancy, and inhibition of ovulation
• PR-A is identical to PR-B except for a 165 amino acid deletion at the N-terminus
• This deletion exposes a 140 amino acid inhibitory domain (ID) that acts as a repressor of steroid hormone transcriptional activity
• In its inactive state, PgR forms a multiprotein complex which includes heat shock proteins and immunophins
• Upon binding of progesterone hormone to its receptor, there is a conformational change that allows dimerization and binding of the receptor to progesterone response elements (PRE) sequences, resulting in activated transcription
• A Null mutation in the PGR gene leads to pleiotrophic reproductive abnormalities.