Independent downstream gene expression profiles in the presence of estrogen receptor alpha or beta

The two known forms of estrogen receptor (ER), alpha and beta, exhibit differences in structure, affinity for certain ligands, and tissue distribution, suggesting differential roles. It is of interest from several perspectives to determine whether the two receptors elicit similar or differing responses within the same cell type in the presence of the same ligand. To evaluate roles of ER, we have examined responses to estrogen in a rat embryonic fibroblast cell line model, normally naive to ER, engineered to stably express ERalpha or ERbeta. Rat1+ERalpha, Rat1+ERbeta, and precursor Rat1 cell lines were treated with estradiol-17beta (E(2); 1 nM) or an ethanol vehicle for 24 h. Total RNA was extracted, and cDNA generated and subjected to suppression subtractive hybridization (SSH), followed by differential screening using dot blot hybridization. In the presence of ERalpha, products were identified that represent classic responses to E(2), including markers for cell proliferation. In the presence of ERbeta, an alternate transcription profile was observed, including upregulation of pro-alpha-2(I) collagen. These data support a model in which ERalpha and ERbeta regulate unique subsets of downstream genes within a given cell type.