Expression and regulation of estrogen receptor beta in human breast tumors and cell lines.
Expression of estrogen receptor beta (ER-beta) and its regulation by estradiol and anti-estrogens was analyzed in breast cancer cells. We determined that ER-beta is expressed in normal and tumor human breast tissue as well as in breast cancer cell lines. We observed moderate levels of ER-beta expression in both T47D and T47D-V22 (a T47D variant cell line) cells, in contrast with T47DCo (a T47D variant cell line) cells when compared to ER-alpha expression. While T47DCo (a T47D variant cell line), BT474, MDA-MB-231, MDA-MB-453, MDA-MB-468 and MCF-7 express low levels of ER-beta, other cell lines including the T47D-Y (a T47D variant cell line), MDA-MB-435, BT-549, and SKBr-3 cells express undetectable levels of ER-beta. Interestingly, ER-beta and ER-alpha are apparently not co-expressed in the breast tissue analyzed. Estradiol induced 30-40-fold increased ER-beta mRNA expression in T47D cells over control untreated cells. Moreover, the anti-estrogen, 4-hydroxy-tamoxifen (4OH-Tam) strongly inhibited estradiol induction of ER-beta expression, but had little or no effect on estradiol induction of ER-alpha. A pure anti-estrogen, ICI-182,780, completely abolished the ability of estradiol to up-regulate the expression of ER. In addition, both actinomycin D and cyclohexymide inhibited estradiol induction of ER-beta mRNA, indicating that de novo mRNA and protein synthesis are probably required for this induction. In summary, this study demonstrates that ER-beta is expressed in breast cancer, and it is regulated by estradiol. Moreover, the studies demonstrate that estradiol up-regulation of ER-beta mRNA in T47D cells can be abolished by anti-estrogens. Thus, ER-beta expression may serve as a prognostic, diagnostic and/or therapeutic marker for breast cancer. To the best of our knowledge, this is the first report regarding hormonal regulation of ER-beta in human mammary cells.
Vladusic
E A
EA
Ernest Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720, USA.
Hornby
A E
AE
Guerra-Vladusic
F K
FK
Lakins
J
J
Lupu
R
R
D001943:Breast Neoplasms / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D000077267:Fulvestrant; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000235:genetics*; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D003609:Dactinomycin; D000077267:Fulvestrant; D004958:Estradiol; D003513:Cycloheximide