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

Oncol Rep. Jan-Feb 2000;7(1):157-67. doi: 10.3892/or.7.1.157.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Cycloheximide / pharmacology
  • Dactinomycin / pharmacology
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Female
  • Fulvestrant
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • RNA, Messenger / analysis
  • Receptors, Estrogen / genetics*
  • Tumor Cells, Cultured

Substances

  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • RNA, Messenger
  • Receptors, Estrogen
  • Dactinomycin
  • Fulvestrant
  • Estradiol
  • Cycloheximide