Inducible upregulation of oestrogen receptor-beta1 affects oestrogen and tamoxifen responsiveness in MCF7 human breast cancer cells

J Mol Endocrinol. 2005 Apr;34(2):553-66. doi: 10.1677/jme.1.01688.


To investigate the effect of altered oestrogen receptor (ER)alpha and ERbeta expression on oestrogen and anti-oestrogen action in breast cancer, we have stably expressed an inducible ERbeta1 in MCF7 breast cancer cells. Stably expressing clones were isolated and over-expression of ERbeta1 correlated with increased levels of specific radiolabelled oestradiol (E2) binding. Increased ERbeta1 did not affect endogenous levels of ERalpha but increased progesterone receptor (PR) levels. Over-expression of ERbeta1 reduced growth responses to E2 in contrast to little if any effect of over-expression of ERalpha. In oestrogen-replete conditions, over-expression of ERbeta1 but not ERalpha reduced proliferation. Over-expression of ERbeta1 did not result in anti-oestrogen resistance but was associated with increased sensitivity to 4-hydroxytamoxifen. Our results suggested that over-expression of ERbeta1 in the presence of an endogenously expressed ERalpha was associated with tamoxifen sensitivity but may negatively modulate ERalpha-mediated growth. However, not all ERalpha activities were inhibited since endogenous PR expression was increased by both ERalpha and ERbeta1 over-expression. These data paralleled those seen in some in vivo studies showing a relationship between PR and ERbeta expression as well as ERbeta expression and tamoxifen sensitivity of ER-positive breast cancer patients. These models are relevant and will be useful for dissecting the role of ERbeta1 expression in ER-positive breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Doxycycline / metabolism
  • Drug Resistance, Neoplasm*
  • Epitopes
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / genetics
  • Estrogen Receptor beta / metabolism*
  • Estrogens / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Molecular Probes / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism
  • Tamoxifen / metabolism*
  • Tamoxifen / therapeutic use
  • Up-Regulation


  • Anti-Bacterial Agents
  • Epitopes
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • Molecular Probes
  • Protein Isoforms
  • Receptors, Progesterone
  • Tamoxifen
  • Doxycycline