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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 4 1601-1605
Copyright © 2000 by The Endocrine Society


Original Studies

Identification of Wild-Type and Exon 5 Deletion Variants of Estrogen Receptor ß in Normal Human Mammary Gland1

Valerie Speirs, Ian P. Adams, David S. Walton and Stephen L. Atkin

Medical Research Laboratory, Wolfson Building, University of Hull, Hull HU6 7RX, United Kingdom

Address correspondence and requests for reprints to: Dr. Valerie Speirs, Molecular Medicine Unit, Clinical Sciences Building, St. James’s University Hospital, Leeds LS9 7TF, United Kindgom. E-mail: v.speirs{at}leeds.ac.uk

We have examined messenger RNA (mRNA) expression of estrogen receptor (ER) {alpha}, wild-type ERß (mRNA and protein), and ERß exon 5 deletion variants (ERß {Delta}5) in samples of normal human mammary gland obtained from 37 premenopausal subjects undergoing reduction mammoplasty. Comparing individual expression, ERß mRNA predominated, expressed in 34 of 37 samples (91%), whereas ER{alpha} was found in 21 of 37 cases (57%). Receptor combinations were then analyzed and compared. Most samples either coexpressed ER{alpha} with ERß (54%) or expressed just ERß (38%). Immunohistochemical analysis revealed that ERß mRNA expression mirrored that of protein. Immunoreactivity was observed in the nucleus with additional evidence of cytoplasmic staining in those epithelial cells lining the breast ducts. Sporadic immunoreactivity was also detected in stromal cells. Expression of wild type and ERß {Delta}5 was analyzed, and their association with ER{alpha} was compared. Most samples coexpressed wild-type ERß and the splice variant (62%; P = 0.05), with 30% exclusively expressing wild-type ERß. Although samples coexpressing wild type and variant ERß showed no statistical association with ER{alpha}, those samples expressing only wild-type ERß, showed a trend toward associations with ER{alpha} (P = 0.07). In conclusion, our data would support a role for ERß in the normal human mammary gland, where we propose it may be the dominant receptor.




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