摘要目的 观察表皮生长因子受体( EGFR)/丝氨酸/苏氨酸蛋白激酶(AKT)途径在三苯氧胺(TAM)耐药人乳腺癌细胞株MCF-7形成过程的变化,及抑制该途径对肿瘤细胞周期的影响.方法 用1×10-7 nmoL/L的三苯氧胺诱导、建立三苯氧胺耐药细胞(TAM-R)细胞株,以荧光定量逆转录聚合酶链反应( fqRT-PCR)、Western blot法、流式细胞术检测MCF-7与TAM-R细胞中EGFR mRNA、p-AKT蛋白的表达及TAM-R细胞给予EGFR及AKT抑制剂后对细胞周期的影响.结果 TAM-R细胞中EGFR mRNA和p-AKT蛋白的表达较MCF-7显著提高(P＜0.05)；给予ZD1839和SH-6阻断EGFR/AKT信号通路后,p-AKT表达受到抑制(P＜0.05),TAM-R细胞的G0～G1期比例提高,其中20 μmol/L ZD1839组高达88％,细胞增殖指数下降(P＜0.05).结论 EGFR/AKT信号通路在MCF-7细胞对TAM耐药的形成中提供了非雌激素途径的生长信号.

abstractsObjective To investigate the change of epidermal growth factor receptor/protein kinase B (EGFR/AKT) signaling pathway in the generation of tamoxifen (TAM) resistant MCF-7 breast cancer cells and the impact on the tumor cell cycle by suppressing EGFR/AKT signaling pathway.Methods The TAM-R was derived from the wild type MCF-7 breast cancer cells continuously exposed to 1 × 10-7 nmol/L 4-hydroxy tamoxifen for 6 months. EGFR mRNA and p-AKT were detected by using fluorescent quantitation reverse transcription-polymerase chain reaction (fqRT-PCR) and Western blotting,respectively.Cell cycle was tested by flow cytometry.Results The expression levels of EGFR mRNA and p-AKT protein in TAM-R cells were higher (P＜0.05) than those in MCF-7 cells.lnhibitors,ZD1839 and SH-6,suppressed the expression of p-AKT and the proliferation of TAM-R cells significantly.Conclusion The activation of EGFR/AKT signaling pathway may provide other growth signal,not estrogen,in tamoxifen resistant MCF-7 cells.