Expression and regulation of estrogen receptor beta in human breast tumorsand cell lines

Expression of estrogen receptor beta (ER-beta) and its regulation by estrad iol and anti-estrogens was analyzed in breast cancer cells. We determined t hat 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-B expressio n in both T47D and T47D-V22 (a T47D variant cell line) cells, in contrast w ith T47DCo (a T47D variant cell line) cells when compared to ER-alpha expre ssion. While T47DCo (a T47D variant cell line), BT474, MDA-MB-231, MDA-MB-4 53, MDA-MB-468 and MCF-7 express low levels of ER-R, other cell lines inclu ding the T47D-Y (a T47D variant cell line), MDA-MB-435, BT-549, and SKBr-3 cells express undetectable levels of ER-D. Interestingly, ER-beta and ER-al pha are apparently not co-expressed in the breast tissue analyzed. Estradio l induced 30-40-fold increased ER-beta mRNA expression in T47D cells over c ontrol untreated cells. Moreover, the anti-estrogen, 4-hydroxy-tamoxifen (4 0H-Tam) strongly inhibited estradiol induction of ER-beta expression, but h ad little or no effect on estradiol induction of ER-alpha. A pure anti-estr ogen, ICI-182,780, completely abolished the ability of estradiol to up-regu late the expression of ER. In addition, both actinomycin D and cyclohexymid e inhibited estradiol induction of ER-beta mRNA, indicating that de novo mR NA and protein synthesis are probably required for this induction. In summa ry, this study demonstrates that ER-beta is expressed in breast cancer, and it is regulated by estradiol. Moreover, the studies demonstrate that estra diol up-regulation of ER-beta mRNA in T47D cells can be abolished by anti-e strogens. Thus, ER-beta expression may serve as a prognostic, diagnostic an d/or therapeutic marker for breast cancer. To the best of our knowledge, th is is the first report regarding hormonal regulation of ER-beta in human ma mmary cells.