Endocrinology, Vol 122, 935-944, Copyright © 1988 by Endocrine Society

ARTICLES

Regulation of progesterone receptor messenger ribonucleic acid and protein levels in MCF-7 cells by estradiol: analysis of estrogen's effect on progesterone receptor synthesis and degradation

AM Nardulli, GL Greene, BW O'Malley and BS Katzenellenbogen
Department of Physiology and Biophysics, University of Illinois, Urbana 61801.

The human breast cancer cell line MCF-7 responds to estrogens with increased progesterone receptor (PR) levels. In this study, we use dense amino acid density shift analyses to address directly the question of whether estrogen increases PR levels in MCF-7 cells by altering rates of receptor synthesis and/or degradation. Using different concentrations of estradiol (E2), which achieve PR levels that are half-maximal (3 X 10(-11) M F2) or maximal (6 X 10(-11) M E2), we have done sucrose gradient density shift analyses using dense (15N, 13C, 2H) amino acid incorporation to study rates of PR synthesis and degradation. These studies reveal a nonlinear loss of preexisting normal density receptor with time. From kinetic modeling analyses, equivalent rates of degradation are estimated for PR whether maximal or half-maximal levels are maintained, indicating that the major effect of E2 on PR content is to increase the rate of PR synthesis while leaving the degradation rate unaltered. The E2-stimulated increase in PR protein is also associated with increased levels of PR mRNA, as demonstrated by the use of a human PR cDNA probe. These density shift data provide evidence that the increased PR levels after estrogen exposure in MCF-7 cells are the result of an increased rate of receptor synthesis, rather than modulation of the rate of receptor degradation.

This article has been cited by other articles:

				H. Yamaguchi, S. Kamiya, T. Uruma, T. Osaki, H. Taguchi, T. Hanawa, M. Fukuda, H. Kawakami, H. Goto, H. Friedman, et al. Chlamydia pneumoniae Growth Inhibition in Cells by the Steroid Receptor Antagonist RU486 (Mifepristone) Antimicrob. Agents Chemother., June 1, 2008; 52(6): 1991 - 1998. [Abstract] [Full Text] [PDF]

				A. K. Rao, Y. S. Ziegler, I. X. McLeod, J. R. Yates, and A. M. Nardulli Effects of Cu/Zn Superoxide Dismutase on Estrogen Responsiveness and Oxidative Stress in Human Breast Cancer Cells Mol. Endocrinol., May 1, 2008; 22(5): 1113 - 1124. [Abstract] [Full Text] [PDF]

				C. D. Curtis, V. S. Likhite, I. X. McLeod, J. R. Yates, and A. M. Nardulli Interaction of the Tumor Metastasis Suppressor Nonmetastatic Protein 23 Homologue H1 and Estrogen Receptor {alpha} Alters Estrogen-Responsive Gene Expression Cancer Res., November 1, 2007; 67(21): 10600 - 10607. [Abstract] [Full Text] [PDF]

				S. El Marzouk, J. R Schultz-Norton, V. S Likhite, I. X McLeod, J. R Yates, and A. M Nardulli Rho GDP dissociation inhibitor {alpha} interacts with estrogen receptor {alpha} and influences estrogen responsiveness J. Mol. Endocrinol., October 1, 2007; 39(4): 249 - 259. [Abstract] [Full Text] [PDF]

				M. D. Aupperlee and S. Z. Haslam Differential Hormonal Regulation and Function of Progesterone Receptor Isoforms in Normal Adult Mouse Mammary Gland Endocrinology, May 1, 2007; 148(5): 2290 - 2300. [Abstract] [Full Text] [PDF]

				B. Kuske, C. Naughton, K. Moore, K. G MacLeod, W. R Miller, R. Clarke, S. P Langdon, and D. A Cameron Endocrine therapy resistance can be associated with high estrogen receptor {alpha} (ER{alpha}) expression and reduced ER{alpha} phosphorylation in breast cancer models Endocr. Relat. Cancer, December 1, 2006; 13(4): 1121 - 1133. [Abstract] [Full Text] [PDF]

				P. Mussi, L. Liao, S.-E. Park, P. Ciana, A. Maggi, B. S. Katzenellenbogen, J. Xu, and B. W. O'Malley Haploinsufficiency of the corepressor of estrogen receptor activity (REA) enhances estrogen receptor function in the mammary gland PNAS, November 7, 2006; 103(45): 16716 - 16721. [Abstract] [Full Text] [PDF]

				J. R. Schultz, L. N. Petz, and A. M. Nardulli Cell- and Ligand-specific Regulation of Promoters Containing Activator Protein-1 and Sp1 Sites by Estrogen Receptors {alpha} and {beta} J. Biol. Chem., January 7, 2005; 280(1): 347 - 354. [Abstract] [Full Text] [PDF]

				M. Widschwendter, K. D. Siegmund, H. M. Muller, H. Fiegl, C. Marth, E. Muller-Holzner, P. A. Jones, and P. W. Laird Association of Breast Cancer DNA Methylation Profiles with Hormone Receptor Status and Response to Tamoxifen Cancer Res., June 1, 2004; 64(11): 3807 - 3813. [Abstract] [Full Text] [PDF]

				L. N. Petz, Y. S. Ziegler, J. R. Schultz, and A. M. Nardulli Fos and Jun Inhibit Estrogen-Induced Transcription of the Human Progesterone Receptor Gene through an Activator Protein-1 Site Mol. Endocrinol., March 1, 2004; 18(3): 521 - 532. [Abstract] [Full Text] [PDF]

				L. N. Petz, Y. S. Ziegler, M. A. Loven, and A. M. Nardulli Estrogen Receptor {alpha} and Activating Protein-1 Mediate Estrogen Responsiveness of the Progesterone Receptor Gene in MCF-7 Breast Cancer Cells Endocrinology, December 1, 2002; 143(12): 4583 - 4591. [Abstract] [Full Text] [PDF]

				S. L. Grimm, T. N. Seagroves, E. B. Kabotyanski, R. C. Hovey, B. K. Vonderhaar, J. P. Lydon, K. Miyoshi, L. Hennighausen, C. J. Ormandy, A. V. Lee, et al. Disruption of Steroid and Prolactin Receptor Patterning in the Mammary Gland Correlates with a Block in Lobuloalveolar Development Mol. Endocrinol., December 1, 2002; 16(12): 2675 - 2691. [Abstract] [Full Text] [PDF]

				E. K. Lobenhofer, L. Bennett, P. L. Cable, L. Li, P. R. Bushel, and C. A. Afshari Regulation of DNA Replication Fork Genes by 17{beta}-Estradiol Mol. Endocrinol., June 1, 2002; 16(6): 1215 - 1229. [Abstract] [Full Text] [PDF]

				L. N. Petz and A. M. Nardulli Sp1 Binding Sites and An Estrogen Response Element Half-Site Are Involved in Regulation of the Human Progesterone Receptor A Promoter Mol. Endocrinol., July 1, 2000; 14(7): 972 - 985. [Abstract] [Full Text]

				R. K. Ross, A. Paganini-Hill, P. C. Wan, and M. C. Pike Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen Versus Estrogen Plus Progestin J Natl Cancer Inst, February 16, 2000; 92(4): 328 - 332. [Abstract] [Full Text] [PDF]

				Z. Nawaz, D. M. Lonard, A. P. Dennis, C. L. Smith, and B. W. O'Malley Proteasome-dependent degradation of the human estrogen receptor PNAS, March 2, 1999; 96(5): 1858 - 1862. [Abstract] [Full Text] [PDF]

				D. M. Tanenbaum, Y. Wang, S. P. Williams, and P. B. Sigler Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains PNAS, May 26, 1998; 95(11): 5998 - 6003. [Abstract] [Full Text] [PDF]

				S. Hild-Petito and A. T. Fazleabas Expression of Steroid Receptors and Steroidogenic Enzymes in the Baboon (Papio anubis) Corpus Luteum during the Menstrual Cycle and Early Pregnancy J. Clin. Endocrinol. Metab., March 1, 1997; 82(3): 955 - 962. [Abstract] [Full Text] [PDF]

				K. K. Leslie, D. Keefe, S. Powell, and F. Naftolin Estrogen Receptors Are Identified in the Glioblastoma Cell Line UI38MG Reproductive Sciences, July 1, 1994; 1(3): 238 - 244. [Abstract] [PDF]