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

• Published in: The journal of clinical endocrinology and metabolism Vol. 85; no. 4; pp. 1601 - 1605
• Main Authors: SPEIRS, V, ADAMS, I. P, WALTON, D. S, ATKIN, S. L
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.04.2000
• Subjects: Adolescent; Adult; Biological and medical sciences; Breast - chemistry; Estrogen Receptor alpha; Estrogen Receptor beta; Exons; Female; Fundamental and applied biological sciences. Psychology; Gene Deletion; Gene Expression; Genetic Variation; Humans; Immunohistochemistry; Mammalian female genital system; Morphology. Physiology; Receptors, Estrogen - analysis; Receptors, Estrogen - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Vertebrates: reproduction; Human; Immunohistochemistry; Pathology; Genetic variant; Estrogen; Breast; Adult; Female; Gene expression; In vitro; Hormonal receptor
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.85.4.1601

We have examined messenger RNA (mRNA) expression of estrogen receptor (ER) alpha, wild-type ERbeta (mRNA and protein), and ERbeta exon 5 deletion variants (ERbeta delta5) in samples of normal human mammary gland obtained from 37 premenopausal subjects undergoing reduction mammoplasty. Comparing individual expression, ERbetaP mRNA predominated, expressed in 34 of 37 samples (91%), whereas ERalpha was found in 21 of 37 cases (57%). Receptor combinations were then analyzed and compared. Most samples either coexpressed ERalpha with ERbeta (54%) or expressed just ERbeta (38%). Immunohistochemical analysis revealed that ERbeta 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 ERbeta delta5 was analyzed, and their association with ERalpha was compared. Most samples coexpressed wild-type ERbeta and the splice variant (62%; P = 0.05), with 30% exclusively expressing wild-type ERbeta. Although samples coexpressing wild type and variant ERbeta showed no statistical association with ERalpha, those samples expressing only wild-type ERP, showed a trend toward associations with ERalpha (P = 0.07). In conclusion, our data would support a role for ERbeta in the normal human mammary gland, where we propose it may be the dominant receptor.