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Submitted on July 23, 2003
Accepted on October 29, 2003
1 Department of Medical Nutrition, Karolinska Institutet, Novum, S-141 86 Huddinge, Sweden.
* To whom correspondence should be addressed. E-mail: Lars-Arne.Haldosen{at}mednut.ki.se.
Mammary gland development involves complex cycles of proliferation, differentiation and morphogenesis, regulated by hormones including estrogens, PRL and epidermal growth factor. The mouse mammary epithelial cell line HC11 has been shown to be valuable for investigations of differentiation of mammary gland. In this study, we show that HC11 cells express ER
and ER
proteins at all developmental stages. We have established two different stable HC11 cell lines; H-ERE containing an ERE-reporter and H-Bc containing a -casein reporter. Transcription of the ERE-reporter was only activated in proliferating cells in the presence of EGF. When the cells entered the differentiation program, in the absence of EGF, E2-induced transcription of the ERE reporter was repressed and similar results were obtained when MAPK signaling was inhibited in proliferating cells. We propose that these findings are related to changes in ER co-repressor levels, regulated by EGF. We also report that the -casein reporter was activated in terminally differentiated cells and that this induction was effectively repressed by E2-treatment. Finally, we show a physical interaction between endogenous ER and STAT5 in differentiated HC11 cells. In summary, our results show that ER functional activity changes during differentiation of HC11 cells.
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