Identification of wild-type and exon 5 deletion variants of estrogen receptor beta in normal human mammary gland

We have examined messenger RNA (mRNA) expression of estrogen receptor (ER) alpha, wild-type ER beta (mRNA and protein), and ER beta exon 5 deletion va riants (ERP Delta 5) in samples of normal human mammary gland obtained from 37 premenopausal subjects undergoing reduction mammoplasty. Comparing indi vidual expression, ER beta mRNA predominated, expressed in 34 of 37 samples (91%), whereas ER alpha was found in 21 of 37 cases (57%). Receptor combin ations were then analyzed and compared. Most samples either coexpressed ER alpha with ER beta (54%) or expressed just ER beta (38%). Immunohistochemic al analysis revealed that ER beta mRNA expression mirrored that of protein. Immunoreactivity was observed in the nucleus with additional evidence of c ytoplasmic staining in those epithelial cells lining the breast ducts. Spor adic immunoreactivity was also detected in stromal cells. Expression of wil d type and ERP Delta 5 was analyzed, and their association with ER alpha wa s compared. Most samples coexpressed wild-type ER beta and the splice varia nt (62%; P = 0.05), with 30% exclusively expressing wild-type ER beta. Alth ough samples coexpressing wild type and variant ER beta showed no statistic al association with ER alpha, those samples expressing only wild-type ER be ta, showed a trend toward associations with ER alpha (P = 0.07). In conclus ion, our data would support a role for ER beta in the normal human mammary gland, where we propose it may be the dominant receptor.