Cross-talk between Stat5b and estrogen receptor-alpha and -beta in mammary epithelial cells.
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.
Björnström
L
L
Department of Cell and Molecular Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Kilic
E
E
Norman
M
M
Parker
M G
MG
Sjöberg
M
M
D000818:Animals; D001483:Base Sequence; D002364:Caseins / Q000235:genetics; D002460:Cell Line; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008894:Milk Proteins; D011401:Promoter Regions, Genetic; D020239:Receptor Cross-Talk; D011960:Receptors, Estrogen / Q000378:metabolism*; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*
D002364:Caseins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008894:Milk Proteins; D011960:Receptors, Estrogen; D050799:STAT5 Transcription Factor; C494096:Stat5b protein, mouse; D015534:Trans-Activators