Endocrinology, Vol 124, 2577-2583, Copyright © 1989 by Endocrine Society

ARTICLES

Autologous down-regulation of messenger ribonucleic acid and protein levels for estrogen receptors in MCF-7 cells: an inverse correlation to progesterone receptor levels

AH Ree, BF Landmark, W Eskild, FO Levy, H Lahooti, T Jahnsen, A Aakvaag and V Hansson
Institute of Medical Biochemistry, University of Oslo, Norway.

In the present study we have examined the effects of estradiol on mRNA levels for estrogen (ER) and progesterone receptors (PR) in the estrogen-dependent mammary carcinoma MCF-7 cell line. The changes in ER immunoactivity and specific binding of [3H]R5020 were also assessed. Estradiol (10(-7) M) caused a transient and time-dependent reduction of the level of mRNA for ER, with a maximal effect (30-40% of control; n = 3) after 72 h. This was associated with a similar decrease in ER immunoactivity. Further treatment (96 and 120 h) revealed a return of ER mRNA to control values, whereas the ER immunoactivity remained depressed. The effect on the mRNA level for PR gave almost the inverse curve. Initially (24-72 h), we observed a pronounced increase in this mRNA, with a maximal effect (6-7 times the control value; n = 3) after 72 h. Treatment beyond 72 h was associated with a gradual return of mRNA for PR toward the control level. The variation in specific binding of [3H]R5020 revealed similar changes, except that changes in specific receptor binding were delayed 24 h compared to the levels of mRNA. Incubation with low concentrations (10(-11) and 10(-10) M) of estradiol for 72 h was associated with slightly elevated levels of mRNA for ER, whereas higher concentrations gave a dose-dependent decrease. The mRNA for PR was biphasically stimulated, with a maximal effect at 10(-10)- 10(-8) M, where a 10- to 13-fold stimulation was observed. The highest concentration (10(-7) M) gave a lower response. Assessment of concentration-induced variations in protein receptor levels of ER and PR reflected the effects of estradiol on their mRNAs. Low concentrations of estradiol slightly enhanced the ER level, whereas high concentrations clearly reduced ER immunoactivity. The PR level was stimulated by all concentrations used, and 10(-8) M estradiol raised the PR level more than 11-fold. Our results indicate autologous regulation of estrogen receptor gene transcripts and proteins and a clear induction of PR mRNA and receptor proteins by estradiol.

This article has been cited by other articles:

				E. T. Alarid Lives and Times of Nuclear Receptors Mol. Endocrinol., September 1, 2006; 20(9): 1972 - 1981. [Abstract] [Full Text] [PDF]

				S A Khan, D Bhandare, and R T Chatterton Jr The local hormonal environment and related biomarkers in the normal breast Endocr. Relat. Cancer, September 1, 2005; 12(3): 497 - 510. [Abstract] [Full Text] [PDF]

				E. T. Alarid, M. T. Preisler-Mashek, and N. M. Solodin Thyroid Hormone Is an Inhibitor of Estrogen-Induced Degradation of Estrogen Receptor-{alpha} Protein: Estrogen-Dependent Proteolysis Is Not Essential for Receptor Transactivation Function in the Pituitary Endocrinology, August 1, 2003; 144(8): 3469 - 3476. [Abstract] [Full Text] [PDF]

				M. S. Cotroneo, J. Wang, W. A. Fritz, I.-E. Eltoum, and C. A. Lamartiniere Genistein action in the prepubertal mammary gland in a chemoprevention model Carcinogenesis, September 1, 2002; 23(9): 1467 - 1474. [Abstract] [Full Text] [PDF]

				M. Fan, X. Long, J. A. Bailey, C. A. Reed, E. Osborne, E. A. Gize, E. A. Kirk, R. M. Bigsby, and K. P. Nephew The Activating Enzyme of NEDD8 Inhibits Steroid Receptor Function Mol. Endocrinol., February 1, 2002; 16(2): 315 - 330. [Abstract] [Full Text] [PDF]

				A. S. Oh, L. A. Lorant, J. N. Holloway, D. L. Miller, F. G. Kern, and D. El-Ashry Hyperactivation of MAPK Induces Loss of ER{alpha} Expression in Breast Cancer Cells Mol. Endocrinol., August 1, 2001; 15(8): 1344 - 1359. [Abstract] [Full Text] [PDF]

				E. K. Lobenhofer, G. Huper, J. D. Iglehart, and J. R. Marks Inhibition of Mitogen-activated Protein Kinase and Phosphatidylinositol 3-Kinase Activity in MCF-7 Cells Prevents Estrogen-induced Mitogenesis Cell Growth Differ., February 1, 2000; 11(2): 99 - 110. [Abstract] [Full Text]

				S. A. Khan, A. Sachdeva, S. Naim, M. M. Meguid, W. Marx, H. Simon, J. D. Halverson, and P. J. Numann The Normal Breast Epithelium of Women with Breast Cancer Displays an Aberrant Response to Estradiol Cancer Epidemiol. Biomarkers Prev., October 1, 1999; 8(10): 867 - 872. [Abstract] [Full Text]

				E. T. Alarid, N. Bakopoulos, and N. Solodin Proteasome-Mediated Proteolysis of Estrogen Receptor: A Novel Component in Autologous Down-Regulation Mol. Endocrinol., September 1, 1999; 13(9): 1522 - 1534. [Abstract] [Full Text]

				M. T. Preisler-Mashek, N. Solodin, B. L. Stark, M. K. Tyriver, and E. T. Alarid Ligand-specific regulation of proteasome-mediated proteolysis of estrogen receptor-alpha Am J Physiol Endocrinol Metab, April 1, 2002; 282(4): E891 - E898. [Abstract] [Full Text] [PDF]