Beta3-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 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.
Saussede-Aim
Jennifer
J
Inserm, U590, Laboratoire de Cytologie Analytique, Faculté de Medecine Rockefeller, Université Lyon 1, Lyon, France. jennifer.saussede-aim@laposte.net
Matera
Eva-Laure
EL
Ferlini
Cristiano
C
Dumontet
Charles
C
D001943:Breast Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D000077267:Fulvestrant; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014404:Tubulin / Q000819:agonists / Q000235:genetics*
D004965:Estrogen Antagonists; D004967:Estrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C498585:TUBB3 protein, human; D014404:Tubulin; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol