ArticleMolecular and cellular biology2008
Progesterone induction of the 11beta-hydroxysteroid dehydrogenase type 2 promoter in breast cancer cells involves coordinated recruitment of STAT5A and progesterone receptor to a distal enhancer and polymerase tracking.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Age-associated genes in human mammary gland drive human breast cancer progression.Breast cancer research : BCR · 2020Article
- The C/ebp-Atf response element (CARE) location reveals two distinct Atf4-dependent, elongation-mediated mechanisms for transcriptional induction of aminoacyl-tRNA synthetase genes in response to amino acid limitation.Nucleic acids research · 2016Article
- Heregulin Co-opts PR Transcriptional Action Via Stat3 Role As a Coregulator to Drive Cancer Growth.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Article
- Post-translational modifications of the progesterone receptors.The Journal of steroid biochemistry and molecular biology · 2014Review
- Lysine methylation of progesterone receptor at activation function 1 regulates both ligand-independent activity and ligand sensitivity of the receptor.The Journal of biological chemistry · 2014Article
- Acetylation at lysine 183 of progesterone receptor by p300 accelerates DNA binding kinetics and transactivation of direct target genes.The Journal of biological chemistry · 2014Article
- Transcriptional complexity and roles of Fra-1/AP-1 at the uPA/Plau locus in aggressive breast cancer.Nucleic acids research · 2014Article
- Progesterone receptor and Stat5 signaling cross talk through RANKL in mammary epithelial cells.Molecular endocrinology (Baltimore, Md.) · 2013Article
- A Common Docking Domain in Progesterone Receptor-B links DUSP6 and CK2 signaling to proliferative transcriptional programs in breast cancer cells.Nucleic acids research · 2013Article
- Research resource: progesterone receptor targetome underlying mammary gland branching morphogenesis.Molecular endocrinology (Baltimore, Md.) · 2013Article
- The biology of progesterone receptor in the normal mammary gland and in breast cancer.Molecular and cellular endocrinology · 2012Review
- Impact of chromatin structure on PR signaling: transition from local to global analysis.Molecular and cellular endocrinology · 2012Review
- Progesterone receptors, their isoforms and progesterone regulated transcription.Molecular and cellular endocrinology · 2012Review
- Control of progesterone receptor transcriptional synergy by SUMOylation and deSUMOylation.BMC molecular biology · 2012Article
- DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors.Molecular biology of the cell · 2012Article
- Minireview: Extranuclear steroid receptors: roles in modulation of cell functions.Molecular endocrinology (Baltimore, Md.) · 2011Review
- Minireview: role of kinases and chromatin remodeling in progesterone signaling to chromatin.Molecular endocrinology (Baltimore, Md.) · 2010Review
- Mutational analysis of progesterone receptor functional domains in stable cell lines delineates sets of genes regulated by different mechanisms.Molecular endocrinology (Baltimore, Md.) · 2009Article
- Mechanisms underlying the control of progesterone receptor transcriptional activity by SUMOylation.The Journal of biological chemistry · 2009Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Steroid hormone receptors regulate gene expression, interacting with target DNA sequences but also activating cytoplasmic signaling pathways. Using the human 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) gene as a model, we have investigated the contributions of both effects on a human progesterone-responsive promoter in breast cancer cells. Chromatin immunoprecipitation has identified two different mechanisms of hormone-induced progesterone receptor (PR) recruitment to the 11beta-HSD2 promoter: (i) direct PR binding to DNA at the proximal promoter, abrogated when PR contains a mutated DNA binding domain (DBD), and (ii) STAT5A (signal transducer and activator of transcription 5A)-mediated recruitment of PR to an upstream distal region, impaired by AG490, a JAK/STAT pathway inhibitor. The JAK/STAT inhibitor, as well as expression of dominant-negative STAT5A, impairs hormone induction of 11beta-HSD2. On the other hand, the DBD-mutated PR fully supports 11beta-HSD2 expression. These results, along with data from a deletion analysis, indicate that the distal region is crucial for hormone regulation of 11beta-HSD2. We show active RNA polymerase II tracking from the distal region upon PR and STAT5A binding, concomitant with synthesis of noncoding, hormone-dependent RNAs, suggesting that this region works as a hormone-dependent transcriptional enhancer. In conclusion, coordination of PR transcriptional effects and cytoplasmic signaling activation, in particular the JAK/STAT pathway, are critical in regulating progestin-induced endogenous 11beta-HSD2 gene expression in breast cancer cells. This is not unique to this promoter, as AG490 also alters the expression of other progesterone-regulated genes.
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