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Gene Review

PGR  -  progesterone receptor

Homo sapiens

Synonyms: NR3C3, Nuclear receptor subfamily 3 group C member 3, PR, Progesterone receptor
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Disease relevance of PGR

  • In contrast, we found no association between any PGR variant or haplotype and breast cancer [1].
  • In conclusion, the lack of association between AR and most clinicopathological features and survival, together with the absence of prognostic value for ER/PGR status, suggest that MBCs are biologically different from female breast carcinomas and make it questionable to use antihormonal therapy for patients with MBC [2].
  • CONLCLUSION: There is predominance of high grade, invasive ductal carcinomas which are likely to be ER and PGR negative but p53 positive [3].
  • Molar pregnancies followed by GTN were associated with higher serum beta-hCG (human chorionic gonadotrophic hormone), larger uterine size for gestational age, negative ER expression, negative PGR expression, and positive telomerase expression [4].
  • When transiently expressed, the two hPR forms similarly activated transcription from reporter genes containing a single palindromic progestin responsive element (PRE), while form B was more efficient at activating the PRE of the mouse mammary tumor virus long terminal repeat [5].

Psychiatry related information on PGR

  • METHODS: We evaluated the impact of age at menarche, pregnancy history, duration of breastfeeding, body mass index, combined oral contraceptive use, and alcohol consumption on breast cancer risk by ER/PR status in 1,725 population-based case patients and 440 control subjects aged 20 to 49 years identified within neighborhoods of case patients [6].
  • Association between a functional polymorphism in the progesterone receptor gene and panic disorder in women [7].
  • For both premenopausal and postmenopausal women, higher recreational physical activity levels (> or = 17.6 MET-hours/week versus no activity) were associated with a 30-60% reduction in risk of nearly all ER/PR subtypes, although the associations were generally of borderline statistical significance [8].
  • Our previous suggestion that progesterone receptor measurements might be a useful marker for hormone dependence in advanced breast cancer is gaining support and may soon have a place in routine therapeutic decision-making [9].
  • Minimal individual differences in size, surface structure and shape, observed between nuclei of malignant epithelium of positive concordant ER and PR status and nuclei of normal epithelium demonstrated that the highest morphological similarity is associated with biochemical similarity of cells exposed to the identical media of steroid hormones [10].

High impact information on PGR

  • The mechanism of RU486 antagonism is dependent on the conformation of the carboxy-terminal tail of the human progesterone receptor [11].
  • The S-phase fraction yielded the most prognostic information, followed by progesterone-receptor status and tumor size [12].
  • Finally, we present evidence that the progesterone receptor acts by facilitating the formation of a stable preinitiation complex at the target gene promoter and thus augments the initiation of transcription by RNA polymerase II [13].
  • Similar transcriptional interference was observed between the endogenous PR and ER present in T47D and MCF-7 breast cancer cells transfected with an ER reporter gene [14].
  • However, despite their insensitivity to estradiol or antiestrogen, PRs are not constitutively synthesized; 5-bromodeoxyuridine and sodium butyrate can selectively inhibit PR production [15].

Chemical compound and disease context of PGR


Biological context of PGR

  • Both the N-terminal A/B region and the hormone binding domain of ER were involved in this inhibition, which was antagonized by antiestrogens and did not appear to involve direct interaction between ER and either reporter gene or PR [14].
  • RESULTS: HR-positive human breast cancer cell lines transfected with the HER-2/neu gene expressed statistically significantly lower levels of ER and PR than parental lines [21].
  • Comparison of the cDNA-deduced amino acid sequence with other PR homologues demonstrated the modular structure characteristic of nuclear receptors [5].
  • Collectively, these results suggest that targeted histone acetylation by recruited HAT cofactors and histone deacetylation are important factors affecting PR transactivation [22].
  • Down-regulation of several members of the protein inhibitors of activated STAT (PIAS) family upon decidualization pointed toward a role of these E3 ligases in PR sumoylation [23].

Anatomical context of PGR

  • Although ER and PGR showed nuclear staining in prostatic epithelium, the overall expression for these receptors was low [24].
  • RESULTS: Overall, white women were significantly more likely to be older and to have smaller tumors, have less lymph node involvement, have tumors with positive ER and PgR status, and have a lower S-phase fraction compared with Hispanic or black women [25].
  • This effect and its reversal in the presence of ligand suggest a novel mechanism, through which hPR can act as a key regulator of both proliferation and differentiation in the human endometrium [26].
  • Expression of human estrogen receptor-alpha and -beta, progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells [27].
  • We have compared the effects of RU486 on PR-dependent transcription in vitro using T47D and HeLa cell nuclear extracts [28].

Associations of PGR with chemical compounds

  • To gain more insight into hormone-responsiveness, estrogen-regulated progesterone receptor (PGR) and androgen-regulated prostatic acid phosphatase (PAP) mRNA levels were also quantified [29].
  • Overall, uPA status appeared independent of association with ER/PgR status in its ability to predict response to tamoxifen treatment [30].
  • RESULTS: MCF-7MDR1 cells retained both estrogen receptor and progesterone receptor expression as well as sensitivity to 4-hydroxytamoxifen [31].
  • Progesterone receptor (PR) functions as a transcription factor that modulates the transcription of target genes in response to progesterone and other signals [32].
  • Furthermore, we show that silencing of PIAS1 not only enhances PR-dependent transcription but also induces expression of prolactin, a decidual marker gene, in progestin-treated HESCs without the need of simultaneous activation of the cAMP pathway [23].

Physical interactions of PGR

  • Here we show that the human PR also interacts with p300/CBP-associated factor in vitro [22].
  • We demonstrate that PIAS1 interacts with the PR and serves as its E3 SUMO ligase upon activation of the receptor [23].
  • Surprisingly, in two cell clones, we found that induction of PR gene expression by ligand-bound ER does not require demethylation of the PR CpG island [33].
  • In a logistic regression model, looking for associations with axillary metastasis, we found a statistically significant interaction between the presence of uPA-PAI-1 complexes and progesterone receptor positivity (P=0.04) [34].
  • RESULTS: Patients with cancers exhibiting advanced stage, high grade, unfavorable tumor histology, nodal involvement, recurrence, and lower PR levels determined by ligand binding had significantly higher uPA content than others [35].

Enzymatic interactions of PGR

  • Human progesterone receptors (PR) are phosphorylated by cyclin-dependent protein kinase 2 (CDK2) at multiple sites, including Ser400 [36].
  • A significant correlation was also seen between estrogen receptor alpha specifically phosphorylated at Ser(118) and progesterone receptor levels (Spearman r = 0.236, P = 0.0118, n = 113) [37].

Regulatory relationships of PGR


Other interactions of PGR


Analytical, diagnostic and therapeutic context of PGR

  • Northern blot analysis of T47D mRNA using various cDNA derived probes identified two classes of hPR mRNAs, one of which could code for hPR form B, while the other one lacked the 5' region upstream of AUG1 [5].
  • Furthermore, depletion of SRC-1/p160 by immunoprecipitation from these transcriptional extracts also significantly impaired PR-mediated RNA synthesis from a naked PRE-linked DNA template [38].
  • Furthermore, a chromatin immunoprecipitation assay demonstrated the hormone-dependent recruitment of UBCH7 onto estrogen receptor- and PR-responsive promoters [44].
  • Assay results for progesterone receptor immunocytochemistry were in agreement (P less than 0.0001) with those of biochemical determination in 74% [45].
  • For PgR H-score, there were statistically significant reductions after treatment with ICI 182,780 125 mg (P = 0.003) and 250 mg (P = 0.0002) compared with placebo [46].


  1. Estrogen receptor genotypes and haplotypes associated with breast cancer risk. Gold, B., Kalush, F., Bergeron, J., Scott, K., Mitra, N., Wilson, K., Ellis, N., Huang, H., Chen, M., Lippert, R., Halldorsson, B.V., Woodworth, B., White, T., Clark, A.G., Parl, F.F., Broder, S., Dean, M., Offit, K. Cancer Res. (2004) [Pubmed]
  2. Androgen receptor expression in male breast carcinoma: lack of clinicopathological association. Pich, A., Margaria, E., Chiusa, L., Candelaresi, G., Dal Canton, O. Br. J. Cancer (1999) [Pubmed]
  3. Clinicopathological features and molecular markers of breast cancer in Jos, Nigeria. Gukas, I.D., Jennings, B.A., Mandong, B.M., Igun, G.O., Girling, A.C., Manasseh, A.N., Ugwu, B.T., Leinster, S.J. West African journal of medicine. (2005) [Pubmed]
  4. Estrogen and progesterone receptors and telomerase enzyme immunohistochemical detection in gestational trophoblastic tumors. El-Shalakany, A.H., Kamel, K.M., Ismail, A.M., Salah, L., El-Deen Fahmy, S.S., El-Deen Ammar, E. Int. J. Gynecol. Cancer (2006) [Pubmed]
  5. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. Kastner, P., Krust, A., Turcotte, B., Stropp, U., Tora, L., Gronemeyer, H., Chambon, P. EMBO J. (1990) [Pubmed]
  6. Hormone-related risk factors for breast cancer in women under age 50 years by estrogen and progesterone receptor status: results from a case-control and a case-case comparison. Ma, H., Bernstein, L., Ross, R.K., Ursin, G. Breast Cancer Res. (2006) [Pubmed]
  7. Association between a functional polymorphism in the progesterone receptor gene and panic disorder in women. Ho, H.P., Westberg, L., Annerbrink, K., Olsson, M., Melke, J., Nilsson, S., Baghaei, F., Rosmond, R., Holm, G., Björntorp, P., Andersch, S., Allgulander, C., Eriksson, E. Psychoneuroendocrinology (2004) [Pubmed]
  8. Body size, physical activity, and breast cancer hormone receptor status: results from two case-control studies. Enger, S.M., Ross, R.K., Paganini-Hill, A., Carpenter, C.L., Bernstein, L. Cancer Epidemiol. Biomarkers Prev. (2000) [Pubmed]
  9. Hormones in breast cancer: update 1978. McGuire, W.L., Horwitz, K.B., Zava, D.T., Garola, R.E., Chamness, G.C. Metab. Clin. Exp. (1978) [Pubmed]
  10. Individual differences between nuclear parameters of normal and malignant breast epithelium. Pikula, B., Savjak, D., Hacker, G.W., Muss, W.H., Amidzic, L., Hauser-Kronberger, C., Malesevic, D., Dietze, O. Zentralbl. Pathol. (1994) [Pubmed]
  11. The mechanism of RU486 antagonism is dependent on the conformation of the carboxy-terminal tail of the human progesterone receptor. Vegeto, E., Allan, G.F., Schrader, W.T., Tsai, M.J., McDonnell, D.P., O'Malley, B.W. Cell (1992) [Pubmed]
  12. Indicators of prognosis in node-negative breast cancer. Sigurdsson, H., Baldetorp, B., Borg, A., Dalberg, M., Fernö, M., Killander, D., Olsson, H. N. Engl. J. Med. (1990) [Pubmed]
  13. The progesterone receptor stimulates cell-free transcription by enhancing the formation of a stable preinitiation complex. Klein-Hitpass, L., Tsai, S.Y., Weigel, N.L., Allan, G.F., Riley, D., Rodriguez, R., Schrader, W.T., Tsai, M.J., O'Malley, B.W. Cell (1990) [Pubmed]
  14. Steroid hormone receptors compete for factors that mediate their enhancer function. Meyer, M.E., Gronemeyer, H., Turcotte, B., Bocquel, M.T., Tasset, D., Chambon, P. Cell (1989) [Pubmed]
  15. Variant T47D human breast cancer cells with high progesterone-receptor levels despite estrogen and antiestrogen resistance. Horwitz, K.B., Mockus, M.B., Lessey, B.A. Cell (1982) [Pubmed]
  16. Decrease in estradiol-stimulated progesterone receptor production in MCF-7 cells by epidermal growth factor and possible clinical implication for paracrine-regulated breast cancer growth. Cormier, E.M., Wolf, M.F., Jordan, V.C. Cancer Res. (1989) [Pubmed]
  17. Changes in estrogen receptor, progesterone receptor, and pS2 expression in tamoxifen-resistant human breast cancer. Johnston, S.R., Saccani-Jotti, G., Smith, I.E., Salter, J., Newby, J., Coppen, M., Ebbs, S.R., Dowsett, M. Cancer Res. (1995) [Pubmed]
  18. Phosphorylation of human progesterone receptor by cyclin-dependent kinase 2 on three sites that are authentic basal phosphorylation sites in vivo. Zhang, Y., Beck, C.A., Poletti, A., Clement, J.P., Prendergast, P., Yip, T.T., Hutchens, T.W., Edwards, D.P., Weigel, N.L. Mol. Endocrinol. (1997) [Pubmed]
  19. Nonsteroidal human progesterone receptor modulators from the marine alga Cymopolia barbata. Pathirana, C., Stein, R.B., Berger, T.S., Fenical, W., Ianiro, T., Mais, D.E., Torres, A., Goldman, M.E. Mol. Pharmacol. (1995) [Pubmed]
  20. Progesterone receptor modulator CDB-2914 down-regulates proliferative cell nuclear antigen and Bcl-2 protein expression and up-regulates caspase-3 and poly(adenosine 5'-diphosphate-ribose) polymerase expression in cultured human uterine leiomyoma cells. Xu, Q., Takekida, S., Ohara, N., Chen, W., Sitruk-Ware, R., Johansson, E.D., Maruo, T. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  21. Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. Konecny, G., Pauletti, G., Pegram, M., Untch, M., Dandekar, S., Aguilar, Z., Wilson, C., Rong, H.M., Bauerfeind, I., Felber, M., Wang, H.J., Beryt, M., Seshadri, R., Hepp, H., Slamon, D.J. J. Natl. Cancer Inst. (2003) [Pubmed]
  22. Steroid receptor induction of gene transcription: a two-step model. Jenster, G., Spencer, T.E., Burcin, M.M., Tsai, S.Y., Tsai, M.J., O'Malley, B.W. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  23. Regulation of the SUMO pathway sensitizes differentiating human endometrial stromal cells to progesterone. Jones, M.C., Fusi, L., Higham, J.H., Abdel-Hafiz, H., Horwitz, K.B., Lam, E.W., Brosens, J.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  24. Cellular distribution of retinoic acid receptor-alpha in benign hyperplastic and malignant human prostates: comparison with androgen, estrogen and progesterone receptor status. Gyftopoulos, K., Sotiropoulou, G., Varakis, I., Barbalias, G.A. Eur. Urol. (2000) [Pubmed]
  25. Tumor biologic factors and breast cancer prognosis among white, Hispanic, and black women in the United States. Elledge, R.M., Clark, G.M., Chamness, G.C., Osborne, C.K. J. Natl. Cancer Inst. (1994) [Pubmed]
  26. Modulation of AP-1 activity by the human progesterone receptor in endometrial adenocarcinoma cells. Bamberger, A.M., Bamberger, C.M., Gellersen, B., Schulte, H.M. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  27. Expression of human estrogen receptor-alpha and -beta, progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells. Lau, K.M., Mok, S.C., Ho, S.M. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  28. Coactivator/corepressor ratios modulate PR-mediated transcription by the selective receptor modulator RU486. Liu, Z., Auboeuf, D., Wong, J., Chen, J.D., Tsai, S.Y., Tsai, M.J., O'Malley, B.W. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  29. Evaluation of androgen, estrogen (ER alpha and ER beta), and progesterone receptor expression in human prostate cancer by real-time quantitative reverse transcription-polymerase chain reaction assays. Latil, A., Bièche, I., Vidaud, D., Lidereau, R., Berthon, P., Cussenot, O., Vidaud, M. Cancer Res. (2001) [Pubmed]
  30. Urokinase-type plasminogen activator and its inhibitor PAI-1: predictors of poor response to tamoxifen therapy in recurrent breast cancer. Foekens, J.A., Look, M.P., Peters, H.A., van Putten, W.L., Portengen, H., Klijn, J.G. J. Natl. Cancer Inst. (1995) [Pubmed]
  31. Effect of P-glycoprotein expression on sensitivity to hormones in MCF-7 human breast cancer cells. Clarke, R., Currier, S., Kaplan, O., Lovelace, E., Boulay, V., Gottesman, M.M., Dickson, R.B. J. Natl. Cancer Inst. (1992) [Pubmed]
  32. Steroid receptor coactivator-1 (SRC-1) enhances ligand-dependent and receptor-dependent cell-free transcription of chromatin. Liu, Z., Wong, J., Tsai, S.Y., Tsai, M.J., O'Malley, B.W. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  33. Demethylation of the progesterone receptor CpG island is not required for progesterone receptor gene expression. Ferguson, A.T., Lapidus, R.G., Davidson, N.E. Oncogene (1998) [Pubmed]
  34. Accumulation of uPA-PAI-1 complexes inside the tumour cells is associated with axillary nodal invasion in progesterone-receptor-positive early breast cancer. Schneider, J., Pollán, M., Tejerina, A., Sánchez, J., Lucas, A.R. Br. J. Cancer (2003) [Pubmed]
  35. Clinical relevance of urokinase-type plasminogen activator, its receptor, and its inhibitor type 1 in endometrial cancer. Tecimer, C., Doering, D.L., Goldsmith, L.J., Meyer, J.S., Abdulhay, G., Wittliff, J.L. Gynecol. Oncol. (2001) [Pubmed]
  36. Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2. Pierson-Mullany, L.K., Lange, C.A. Mol. Cell. Biol. (2004) [Pubmed]
  37. Phospho-serine-118 estrogen receptor-alpha expression is associated with better disease outcome in women treated with tamoxifen. Murphy, L.C., Niu, Y., Snell, L., Watson, P. Clin. Cancer Res. (2004) [Pubmed]
  38. E1A-mediated repression of progesterone receptor-dependent transactivation involves inhibition of the assembly of a multisubunit coactivation complex. Xu, Y., Klein-Hitpass, L., Bagchi, M.K. Mol. Cell. Biol. (2000) [Pubmed]
  39. Genetic instability and the development of steroid hormone insensitivity in cultured T 47D human breast cancer cells. Reddel, R.R., Alexander, I.E., Koga, M., Shine, J., Sutherland, R.L. Cancer Res. (1988) [Pubmed]
  40. Estrogen receptor beta is coexpressed with ERalpha and PR and associated with nodal status, grade, and proliferation rate in breast cancer. Järvinen, T.A., Pelto-Huikko, M., Holli, K., Isola, J. Am. J. Pathol. (2000) [Pubmed]
  41. Sumoylation of the progesterone receptor and of the steroid receptor coactivator SRC-1. Chauchereau, A., Amazit, L., Quesne, M., Guiochon-Mantel, A., Milgrom, E. J. Biol. Chem. (2003) [Pubmed]
  42. Identification of protein arginine methyltransferase 2 as a coactivator for estrogen receptor alpha. Qi, C., Chang, J., Zhu, Y., Yeldandi, A.V., Rao, S.M., Zhu, Y.J. J. Biol. Chem. (2002) [Pubmed]
  43. Functional interaction of hybrid response elements with wild-type and mutant steroid hormone receptors. Truss, M., Chalepakis, G., Slater, E.P., Mader, S., Beato, M. Mol. Cell. Biol. (1991) [Pubmed]
  44. The ubiquitin-conjugating enzyme UBCH7 acts as a coactivator for steroid hormone receptors. Verma, S., Ismail, A., Gao, X., Fu, G., Li, X., O'Malley, B.W., Nawaz, Z. Mol. Cell. Biol. (2004) [Pubmed]
  45. Immunocytochemical localization of estrogen and progesterone receptor and prognosis in human primary breast cancer. Reiner, A., Neumeister, B., Spona, J., Reiner, G., Schemper, M., Jakesz, R. Cancer Res. (1990) [Pubmed]
  46. Comparison of the short-term biological effects of 7alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-3,17beta-diol (Faslodex) versus tamoxifen in postmenopausal women with primary breast cancer. Robertson, J.F., Nicholson, R.I., Bundred, N.J., Anderson, E., Rayter, Z., Dowsett, M., Fox, J.N., Gee, J.M., Webster, A., Wakeling, A.E., Morris, C., Dixon, M. Cancer Res. (2001) [Pubmed]
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