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Effects of estrogen receptor β on resistance to tamoxifen-based endocrine therapy of human breast cancer
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Abstract:
Objective: To investigate the relationship between the expression of estrogen receptorβand endocrine resistance to tamoxifen (TAM) in breast cancer. Methods: Human breast cancer MCF-7 cells transfected with ERα or ER β constructs, M/HK (negative control), M/siα (ERαhigh/ERβlow), and M/siβ (ERαhigh/ERβlow), respectively, were used. The resistance of these transfected cells to TAM was assessed by MTT assay, mRNA levels of the major drug-resistance related genes (MDR1, TOPOⅡ, LRP, and GST- π) by RT-PCR, and levels of p-Akt, p-ERK and PI3K/Akt (major components of the signaling pathways involved in drug-resistance) by Western blotting. Results: Compared with MCF-7 expressing M/HK, cells expressing ER βshowed enhanced proliferation inhibition mediated by TAM in a dose-dependent manner (P<0.05) : (45.788±1.641)% vs (24.288±1.170)% at 1 μmol/L， (57.899±1.583)% vs (31.499±1.978)% at 5 μmol/L, and (59.853±1.648)% vs (38.039±1.482)% at 10 μmol/L, had significantly lower (P<0.05) mRNA levels of MDR1 (0.431±0.032 vs 0.932±0.083), TOPOⅡ (0.234±0.008 vs 0.391±0.002), and LRP (0.47±0.028 vs 0.586±0.036), and had significantly decreased (P<0.05) levels of p-Akt (0.224±0.006) vs (0.437±0.007) and p-ERK (0.367±0.015 vs 0.756±0.039). Conclusion: ER β may alter the resistance of human breast cancer cells to TAM, possibly through down-regulating the expression of drug-resistance genes and activating PI3K/AKT and ERK signal pathways.
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Projects supported by the National Natural Science Foundation of China（No. 81273552，No.30901985）
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