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Differential activation of the IkappaBalpha and mouse mammary tumor virus promoters by progesterone and glucocorticoid receptors.
J Steroid Biochem Mol Biol. 2002 Aug; 81(4-5):309-17.JS

Abstract

The glucocorticoid and progesterone receptors (GR and PR) are structurally homologous and bind a common hormone response element (HRE). The mechanisms by which receptors activate specific promoters when multiple steroids are present in a cell is a critical question in endocrinology. To investigate how co-existing steroid receptors regulate gene transcription, we have compared two hormone-responsive promoters in T47D/A1-2 human breast cancer cells expressing both the GR and PR. The promoters chosen were those for the mouse mammary tumor virus (MMTV) and the gene for IkappaBalpha, the inhibitor of the ubiquitous transcription factor, nuclear factor kappa B (NFkappaB). Several differences between glucocorticoid and progestin activation of the IkappaBalpha and MMTV promoters were revealed. Both steroids activated the endogenous IkappaBalpha promoter, while only glucocorticoids activated a stably integrated MMTV promoter. In combination, progestins enhanced glucocorticoid activation of IkappaBalpha, but antagonized glucocorticoid activation of MMTV. These differences in steroid receptor competition were further demonstrated when levels of the PR were reduced by prolonged treatment with progestin. Under these conditions, the PR no longer competes effectively with the GR for activation of the MMTV promoter. However, on the IkappaBalpha promoter, the GR and PR still activate the promoter in a cooperative fashion. Another difference between the two promoters is their chromatin structure. In this cell line, the MMTV promoter chromatin is "closed" and insensitive to restriction enzyme cleavage, while the IkappaBalpha promoter is "open." Using PR antagonists, we demonstrate that at least one cofactor complex, the BRG-1 chromatin remodeling complex, differentially contributes to activation of both promoters.

Authors+Show Affiliations

Chromatin and Gene Expression Section, National Institute of Environmental Health Sciences, National Institutes of Health, 111 Alexander Drive, MD 27709, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12361720

Citation

Deroo, Bonnie J., and Trevor K. Archer. "Differential Activation of the IkappaBalpha and Mouse Mammary Tumor Virus Promoters By Progesterone and Glucocorticoid Receptors." The Journal of Steroid Biochemistry and Molecular Biology, vol. 81, no. 4-5, 2002, pp. 309-17.
Deroo BJ, Archer TK. Differential activation of the IkappaBalpha and mouse mammary tumor virus promoters by progesterone and glucocorticoid receptors. J Steroid Biochem Mol Biol. 2002;81(4-5):309-17.
Deroo, B. J., & Archer, T. K. (2002). Differential activation of the IkappaBalpha and mouse mammary tumor virus promoters by progesterone and glucocorticoid receptors. The Journal of Steroid Biochemistry and Molecular Biology, 81(4-5), 309-17.
Deroo BJ, Archer TK. Differential Activation of the IkappaBalpha and Mouse Mammary Tumor Virus Promoters By Progesterone and Glucocorticoid Receptors. J Steroid Biochem Mol Biol. 2002;81(4-5):309-17. PubMed PMID: 12361720.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential activation of the IkappaBalpha and mouse mammary tumor virus promoters by progesterone and glucocorticoid receptors. AU - Deroo,Bonnie J, AU - Archer,Trevor K, PY - 2002/10/4/pubmed PY - 2002/12/3/medline PY - 2002/10/4/entrez SP - 309 EP - 17 JF - The Journal of steroid biochemistry and molecular biology JO - J Steroid Biochem Mol Biol VL - 81 IS - 4-5 N2 - The glucocorticoid and progesterone receptors (GR and PR) are structurally homologous and bind a common hormone response element (HRE). The mechanisms by which receptors activate specific promoters when multiple steroids are present in a cell is a critical question in endocrinology. To investigate how co-existing steroid receptors regulate gene transcription, we have compared two hormone-responsive promoters in T47D/A1-2 human breast cancer cells expressing both the GR and PR. The promoters chosen were those for the mouse mammary tumor virus (MMTV) and the gene for IkappaBalpha, the inhibitor of the ubiquitous transcription factor, nuclear factor kappa B (NFkappaB). Several differences between glucocorticoid and progestin activation of the IkappaBalpha and MMTV promoters were revealed. Both steroids activated the endogenous IkappaBalpha promoter, while only glucocorticoids activated a stably integrated MMTV promoter. In combination, progestins enhanced glucocorticoid activation of IkappaBalpha, but antagonized glucocorticoid activation of MMTV. These differences in steroid receptor competition were further demonstrated when levels of the PR were reduced by prolonged treatment with progestin. Under these conditions, the PR no longer competes effectively with the GR for activation of the MMTV promoter. However, on the IkappaBalpha promoter, the GR and PR still activate the promoter in a cooperative fashion. Another difference between the two promoters is their chromatin structure. In this cell line, the MMTV promoter chromatin is "closed" and insensitive to restriction enzyme cleavage, while the IkappaBalpha promoter is "open." Using PR antagonists, we demonstrate that at least one cofactor complex, the BRG-1 chromatin remodeling complex, differentially contributes to activation of both promoters. SN - 0960-0760 UR - https://www.unboundmedicine.com/medline/citation/12361720/Differential_activation_of_the_IkappaBalpha_and_mouse_mammary_tumor_virus_promoters_by_progesterone_and_glucocorticoid_receptors_ DB - PRIME DP - Unbound Medicine ER -