Cross-talk between Stat5b and estrogen receptor-alpha and -beta in mammary epithelial cells
| Autor: | L Bjornstrom, M G Parker, Eser Kilic, M Sjoberg, Michael A. Norman |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.drug_class
Estrogen receptor Cell Line Mice Estrogen-related receptor alpha Mammary Glands Animal Endocrinology Transcription (biology) STAT5 Transcription Factor medicine Animals Estrogen Receptor beta Promoter Regions Genetic Molecular Biology Estrogen receptor beta DNA Primers Base Sequence Estrogen Receptor alpha Caseins Epithelial Cells Receptor Cross-Talk Milk Proteins Prolactin Cell biology DNA-Binding Proteins Receptors Estrogen Estrogen Trans-Activators Signal transduction Estrogen receptor alpha hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of Molecular Endocrinology. 27:93-106 |
| ISSN: | 1479-6813 0952-5041 |
| DOI: | 10.1677/jme.0.0270093 |
| Popis: | Both 17beta-estradiol and prolactin play important roles in the mammary gland, raising the possibility of functional cross-talk between the two signaling pathways. Here, we demonstrate that estrogen receptor-alpha (ERalpha) and -beta (ERbeta) are both able to potentiate transcription from a Stat5-responsive promoter when activated by prolactin. Potentiation was observed not only in the presence of 17beta-estradiol, but also in the presence of anti-estrogens such as tamoxifen and ICI 182,780. The magnitude of the response was dependent on cell-type: in the HC11 mouse mammary epithelial cell line ERbeta potentiates transcription efficiently whereas ERalpha showed low activity. Conversely, in COS-7 cells, both estrogen receptors were active. We show that activation domains in the N-terminus (AF-1) and the C-terminus (AF-2) of the ERs are dispensable for potentiation. The effects are dependent on the presence of an intact DNA-binding/hinge domain, which we show is capable of interacting with Stat5b in vitro and in HC11 cell extracts. We conclude that ERalpha and ERbeta act as coactivators for Stat5b through a mechanism which is independent of AF-1 and AF-2. |
| Databáze: | OpenAIRE |
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