This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wei, L. L. Articles by Miner, R. Search for Related Content PubMed PubMed Citation Articles by Wei, L. L. Articles by Miner, R.

Evidence for the Existence of a Third Progesterone Receptor Protein in Human Breast Cancer Cell Line T47D¹

Department of Medicine [L. L. W., R. M.] and of Cellular and Molecular Physiology [L. L. W.], Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033

² To whom requests for reprints should be addressed, at Division of Endocrinology, Pennsylvania State University College of Medicine, P. O. Box 850, Hershey, PA 17033.

We have used a new monoclonal antibody, designated C-262, directed against the last 14 amino acids of the carboxy-terminus of human progesterone receptors (N. L. Weigel et al., Mol. Endocrinol., 6:1585–1597, 1992) to analyze progesterone receptor structure. This new antibody recognizes the previously described B-receptors (M_r 120,000) and the naturally occurring N-terminal truncated A-receptor (M_r 94,000). In addition to B-and A-receptors, C-262 detects a third progestin-binding protein with a molecular weight of approximately 60,000 in the progestin-responsive human breast cancer cell line, T47D. The 60,000 dalton protein is pre-dominantly found in the cytosolic fraction of untreated T47D cells and binds tightly to the nucleus following progesterone or R5020 treatment of T47D cells. These dynamics are similar to the previously described progesterone receptor isoforms. The 60,000 dalton protein binds the synthetic progestin, [³H]R5020, which competes with cold R5020 as determined with the technique of in situ photoaffinity labeling. Prolonged incubation of nuclear extracts at elevated temperatures does not result in accumulation of the 60,000 dalton protein, yet the level of photoaffinity-labeled B-and A-receptors declines. These data support our hypothesis that the 60,000 dalton protein is not a degradation product of the two larger progesterone receptor isoforms but a distinct progestin-binding protein. This is further supported by our previous study identifying at least two progesterone receptor mRNAs that do not code B- or A-receptors. These two transcripts are not unique to T47D cells and also are present in human breast cancer cells, MCF-7, and normal human endometrium. Taken together, these data provide evidence for the existence of a third progesterone receptor isoform in progestin-responsive tissues.

¹ This work was supported by Grants HD 29793 and CA 40011 from the NIH and MCB 9210584 from the National Science Foundation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 10/ 4/93. Accepted 11/24/93.

This article has been cited by other articles:

				M. A. Behera, Q. Dai, R. Garde, C. Saner, E. Jungheim, and T. M. Price Progesterone stimulates mitochondrial activity with subsequent inhibition of apoptosis in MCF-10A benign breast epithelial cells Am J Physiol Endocrinol Metab, November 1, 2009; 297(5): E1089 - E1096. [Abstract] [Full Text] [PDF]

				B. Gellersen, M.S. Fernandes, and J.J. Brosens Non-genomic progesterone actions in female reproduction Hum. Reprod. Update, January 1, 2009; 15(1): 119 - 138. [Abstract] [Full Text] [PDF]

				A. Samalecos and B. Gellersen Systematic Expression Analysis and Antibody Screening Do Not Support the Existence of Naturally Occurring Progesterone Receptor (PR)-C, PR-M, or Other Truncated PR Isoforms Endocrinology, November 1, 2008; 149(11): 5872 - 5887. [Abstract] [Full Text] [PDF]

				A. A. Merlino, T. N. Welsh, H. Tan, L. J. Yi, V. Cannon, B. M. Mercer, and S. Mesiano Nuclear Progesterone Receptors in the Human Pregnancy Myometrium: Evidence that Parturition Involves Functional Progesterone Withdrawal Mediated by Increased Expression of Progesterone Receptor-A J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1927 - 1933. [Abstract] [Full Text] [PDF]

				C M. Luetjens, A. Didolkar, S. Kliesch, W. Paulus, A. Jeibmann, W. Bocker, E. Nieschlag, and M. Simoni Tissue expression of the nuclear progesterone receptor in male non-human primates and men. J. Endocrinol., June 1, 2006; 189(3): 529 - 539. [Abstract] [Full Text] [PDF]

				H. N. Jabbour, R. W. Kelly, H. M. Fraser, and H. O. D. Critchley Endocrine Regulation of Menstruation Endocr. Rev., February 1, 2006; 27(1): 17 - 46. [Abstract] [Full Text] [PDF]

				P.B. Marshburn, J. Zhang, Z.B. Mostafavi, M.L. Matthews, J. White, and B.S. Hurst Variant progesterone receptor mRNAs are co-expressed with the wild-type progesterone receptor mRNA in human endometrium during all phases of the menstrual cycle Mol. Hum. Reprod., November 1, 2005; 11(11): 809 - 815. [Abstract] [Full Text] [PDF]

				C. Shah, D. Modi, G. Sachdeva, S. Gadkar, and C. Puri Coexistence of Intracellular and Membrane-Bound Progesterone Receptors in Human Testis J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 474 - 483. [Abstract] [Full Text] [PDF]

				X. Li and B. W. O'Malley Unfolding the Action of Progesterone Receptors J. Biol. Chem., October 10, 2003; 278(41): 39261 - 39264. [Full Text] [PDF]

				B. H. Welter, E. L. Hansen, K. J. Saner, Y. Wei, and T. M. Price Membrane-bound Progesterone Receptor Expression in Human Aortic Endothelial Cells J. Histochem. Cytochem., August 1, 2003; 51(8): 1049 - 1055. [Abstract] [Full Text]

				X. Fang, S. Wong, and B. F. Mitchell Messenger RNA for progesterone receptor isoforms in the late-gestation rat uterus Am J Physiol Endocrinol Metab, December 1, 2002; 283(6): E1167 - E1172. [Abstract] [Full Text] [PDF]

				F. A. Patel and J. R. G. Challis Cortisol/Progesterone Antagonism in Regulation of 15-Hydroxysteroid Dehydrogenase Activity and mRNA Levels in Human Chorion and Placental Trophoblast Cells at Term J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 700 - 708. [Abstract] [Full Text] [PDF]

				K. W. Cheng, C.-K. Cheng, and P. C. K. Leung Differential Role of PR-A and -B Isoforms in Transcription Regulation of Human GnRH Receptor Gene Mol. Endocrinol., December 1, 2001; 15(12): 2078 - 2092. [Abstract] [Full Text] [PDF]

				J. J. Li, S. J. Weroha, M. F. Davis, O. Tawfik, X. Hou, and S. A. Li ER and PR in Renomedullary Interstitial Cells During Syrian Hamster Estrogen-Induced Tumorigenesis: Evidence for Receptor-Mediated Oncogenesis Endocrinology, September 1, 2001; 142(9): 4006 - 4014. [Abstract] [Full Text] [PDF]

				M. Luconi, L. Bonaccorsi, M. Maggi, P. Pecchioli, C. Krausz, G. Forti, and E. Baldi Identification and Characterization of Functional Nongenomic Progesterone Receptors on Human Sperm Membrane J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 877 - 885. [Abstract] [Full Text]