Effects of the antiestrogens tamoxifen and raloxifene on the estrogen receptor transactivation machinery

Anticancer Res. 2006 Jan-Feb;26(1B):735-44.

Abstract

The influence of 17beta-estradiol (E2), tamoxifen (TAM) and raloxifen (RLX) on the proliferation of breast (BC) and endometrial carcinoma cell lines (EC) and the expression of different compounds of the estrogen receptor (ER)-transactivation machinery were studied. E2 stimulated the proliferation of BC, but had no effect on the EC. TAM showed a biphasic effect on ER-positive cell lines. RLX showed an antagonistic suppression or no effect. The expression of ERalpha was down-regulated by E2, but not affected by selective estrogen receptor modulators. ERbeta and progesterone receptor expressions were up-regulated by E2, TAM and OHT. This supports the hypothesis that ERbeta expression is also regulated via the ERalpha-pathway. The steroid receptor coactivator (SRC) AIB1 expression was slightly decreased by E2 but not by antiestrogens (antiE). TIF2 expression was increased by E2, TAM and RLX, but SRC-1 expression was not. In comparison, the expressions of ERbeta and progesterone receptor were strongly influenced by antiE, while the expression of SRCs was only slightly affected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Endometrial Neoplasms / drug therapy
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology
  • Estradiol / pharmacology
  • Estrogen Receptor Modulators / pharmacology*
  • Female
  • Humans
  • Raloxifene Hydrochloride / pharmacology*
  • Receptors, Estrogen / biosynthesis*
  • Receptors, Estrogen / genetics
  • Receptors, Progesterone / biosynthesis
  • Receptors, Progesterone / genetics
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / pharmacology*
  • Transcriptional Activation / drug effects*

Substances

  • Estrogen Receptor Modulators
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen
  • Raloxifene Hydrochloride
  • Estradiol