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  • Title: Beta3-tubulin is induced by estradiol in human breast carcinoma cells through an estrogen-receptor dependent pathway.
    Author: Saussede-Aim J, Matera EL, Ferlini C, Dumontet C.
    Journal: Cell Motil Cytoskeleton; 2009 Jul; 66(7):378-88. PubMed ID: 19466750.
    Abstract:
    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.
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