Microtubules are involved in a variety of essential cell functions. Their role during mitosis has made them a target for anti-cancer drugs. However development of resistance has limited their use. It has been established that enhanced beta3-tubulin expression is correlated with reduced response to antimicrotubule agent-based chemotherapy or worse outcome in a variety of tumor settings. However little is known regarding the regulation of beta3-tubulin expression. We investigated the regulatory mechanisms of expression of beta3-tubulin in the MCF-7 cell line, a model of hormone-dependent breast cancer. Exposure of MCF-7 cells to estradiol was found to induce beta3-tubulin mRNA as well as beta3-tubulin protein expression. Conversely, we did not observe induction of beta3-tubulin mRNA by estradiol in MDA-MB-231 cells which are negative for the estrogen receptor (ER). In order to determine whether beta3-tubulin up-regulation is mediated through the ER pathway, MCF-7 cells were exposed to two ER modulators. Exposure to tamoxifen, a selective estrogen receptor modulator, completely abolished the beta3-tubulin mRNA induction due to estradiol in MCF-7 cells. This result was confirmed with fulvestrant, a pure antagonist of ER. These results demonstrate that the effect of estradiol on beta3-tubulin transcription is mediated through an ER dependent pathway.
(c) 2009 Wiley-Liss, Inc.