A variant of human estrogen receptor-α, hER-α36 weakens docetaxel drug efficacy against human breast cancer cell line MCF-7

Abstract

ObjectivehER-α36 is a variant of estrogen receptor-α, identified and cloned by a team of American. This research is to determine whether hER-α36 can enhance or weaken chemosensitivity to docetaxel in breast cancer cell line MCF-7(ERα66 positive).MethodsRT-PCR was used to detect the expressions of ERα66 and ERα36 in the two human breast cancer cell lines MCF-7(MCF-7/ERα66)and MCF-7 transfected with ERα36(MCF-7/ERα36). The two cell lines were treated with docetaxel(0∼100µmol/L), and cell growth and apoptosis were evaluated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay (using adriamycin (0∼50µmol/L)as the control) and flowcytometry. Western blot analysis was used to measure the effect of docetaxel on phosphor-ERK1/2 expression in the two cell lines.ResultsThe expressions of ERα36 and ERα66 were detectable in both MCF-7/ERα66 and MCF-7/ERα36 cell lines, while the expression of ERα36 in MCF-7/ER36 cells was higher. Both docetaxel and adriamycin inhibited the proliferation of both cells lines in a dose and time dependent manner. In comparison with MCF-7/ERα36 cell line, the MCF-7/ERα66 cells produced greater growth inhibition and apoptosis after treatment with docetaxel, but there was no significant difference in growth inhibition between the two cell lines treated with adriamycin; The MCF-7/ERα36 cell line resulted in a significant activation (phosphorylation) of ERK1/2 after treatment with docetaxel in a dose-dependent manner, but in the MCF-7/ERα66 cell line, a decrease in the level of phosphor-ERK1/2 expression was observed as the dose of docetaxel increased.ConclusionERα36 may be an agent that weakens chemosensitivity to docetaxel in breast cancer, probably by activating the expression of ERK1/2.