Progesterone Receptor Recombinant Rabbit Monoclonal Antibody [JF0549]

Function

PR, a protein with 946 amino acids, is a ligand-activated transcription factor member of the steroid receptor super family of nuclear receptors. The functional structure is similar to that of estrogen receptor (ER), with considerable sequence homology in the DNA-binding central domain. PR is predominantly expressed in tumours of female sex steroid responsive tissues such as the mammary gland, endometrium and the ovary. About half of the breast carcinomas are ER+/PR+. A small fraction (<5%) is ER-/PR+. About half of the non-mucinous ovarian carcinomas are also PR+. From other PR-expressing tumours, meningiomas, various pancreatic neoplasms such as solid-pseudopapillary tumour and endocrine tumours, and salivary gland neoplasms are worth mentioning. The ER and PR status has been used for over 20 years as a predictor of breast carcinoma responsiveness to endocrine therapy and as a prognostic indicator for early recurrence. Up to 75% of ER+/PR+ breast carcinomas respond positively to endocrine treatment. ER+/PR- tumours are less responsive, and thus PR status adds information to ER-status. In combination the two predict benefit from endocrine therapy both in adjuvant setting and in advanced disease. In breast cancer predominance of one isoform, namely PR-B, is common. The majority of endometrial carcinomas express only one isoform. The applications of antibodies to PR are similar to those against ER, i.e. diagnosis of PR-positive tumours (often metastasis) and prediction of therapeutic response of breast carcinoma.

Background References

1. Bondi CD et al. The effect of estradiol, progesterone, and melatonin on estrous cycling and ovarian aromatase expression in intact female mice. Eur J Obstet Gynecol Reprod Biol 174:80-5 (2014).

2. Yu Y et al. Prostate stromal cells express the progesterone receptor to control cancer cell mobility. PLoS One 9:e92714 (2014).

Sequence Similarity

Belongs to the nuclear hormone receptor family. NR3 subfamily.

Tissue Specificity

In reproductive tissues the expression of isoform A and isoform B varies as a consequence of developmental and hormonal status. Isoform A and isoform B are expressed in comparable levels in uterine glandular epithelium during the proliferative phase of the menstrual cycle. Expression of isoform B but not of isoform A persists in the glands during mid-secretory phase. In the stroma, isoform A is the predominant form throughout the cycle. Heterogeneous isoform expression between the glands of the endometrium basalis and functionalis is implying region-specific responses to hormonal stimuli.

Post-translational Modification

Phosphorylated on multiple serine sites. Several of these sites are hormone-dependent. Phosphorylation on Ser-294 occurs preferentially on isoform B, is highly hormone-dependent and modulates ubiquitination and sumoylation on Lys-388. Phosphorylation on Ser-102 and Ser-345 also requires induction by hormone. Basal phosphorylation on Ser-81, Ser-162, Ser-190 and Ser-400 is increased in response to progesterone and can be phosphorylated in vitro by the CDK2-A1 complex. Increased levels of phosphorylation on Ser-400 also in the presence of EGF, heregulin, IGF, PMA and FBS. Phosphorylation at this site by CDK2 is ligand-independent, and increases nuclear translocation and transcriptional activity. Phosphorylation at Ser-162 and Ser-294, but not at Ser-190, is impaired during the G(2)/M phase of the cell cycle. Phosphorylation on Ser-345 by ERK1/2 MAPK is required for interaction with SP1.; Sumoylation is hormone-dependent and represses transcriptional activity. Sumoylation on all three sites is enhanced by PIAS3. Desumoylated by SENP1. Sumoylation on Lys-388, the main site of sumoylation, is repressed by ubiquitination on the same site, and modulated by phosphorylation at Ser-294.; Ubiquitination is hormone-dependent and represses sumoylation on the same site. Promoted by MAPK-mediated phosphorylation on Ser-294.; Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation.

Subcellular Location

Nucleus, Cytoplasm, Mitochondrion outer membrane.

UNIPROT

SwissProt: P06401 Human

Synonyms

NR3C3 antibody

Nuclear receptor subfamily 3 group C member 3 antibody

PGR antibody

PR antibody

PRA antibody

PRB antibody

PRGR_HUMAN antibody

Progesterone receptor antibody

Progestin receptor form A antibody

Progestin receptor form B antibody