Regulation of gene expression by estrogen in mammary gland of wild type and estrogen receptor alpha knockout mice.

Using serial analysis of gene expression, we examined the effects of estrogen (E2) replacement in gonadectomized wild type (WT) and E2 receptor alpha knockout (ERalphaKO) mice on global gene expression in mammary gland. In WT mice, a total of 429,302 tags were sequenced, representing the expression level of 99,854 tag species. A total of ten transcripts were found to be modulated by E2, such as sorting nexin 5 and two no match tags. In the ERalphaKO mice, a total of 459,439 tags were sequenced, representing the expression level of 120,149 tag species. Interestingly, the same three transcripts were inversely regulated by E2 in ERalphaKO mice. In total, 78 transcripts were upregulated by E2, while 29 transcripts were downregulated. In contrast to WT mice, the majority of transcripts related to immunity were repressed in ERalphaKO mice. Moreover, induction of transcripts involved in cell differentiation, Ca2+ response, cytoskeleton, protein biosynthesis and secretion, glycolysis, and oxidative phosphorylation were seen only in ERalphaKO mice. The current study will provide useful information to understand the cellular mechanisms of E(2)-mediated gene regulation in tissues in vivo for the development of novel drugs targeting specific ER action in pathological conditions.