β3-Tubulin is Induced by Estradiol in Human Breast Carcinoma Cells Through an Estrogen-Receptor Dependent Pathway

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 beta 3-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 beta 3-tubulin expression. We investigated the regulatory mechanisms of expression of beta 3-tubulin in the MCF-7 cell line, a model of lion-none-dependent breast cancer. Exposure of MCF-7 cells to estradiol was found to induce beta 3-tubulin mRNA as well as beta 3-tubulin protein expression. Conversely, we did not observe induction of beta 3-tubulin mRNA by estradiol in MDA-MB-231 cells which are negative for the estrogen receptor (ER). In order to determine whether beta 3-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 beta 3-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 beta 3-tubulin transcription is mediated through an ER dependent pathway. Cell Motil. Cytoskeleton 66: 378-388, 2009. (C) 2009 Wiley-Liss, Inc.