卵巢癌细胞ER亚型和p160共激活因子表达及其与他莫西芬和雌激素敏感相关性

Relationship between the expressions of estrogen receptor isoforms and p160 coactivitors in epithelial ovarian cancer cell lines and their sensitivity to tamoxifen and estrogen

目的:分析比较4种常见的人上皮性卵巢癌细胞系(A2780、CAOV-3、SKOV-3和ES-2)雌激素受体(ER)亚型及p160共激活因子表达及其对他莫西芬(TAM)和雌激素敏感性的关系。方法:采用免疫印迹法和RT-PCR技术检测ERα、ERβ及p160共激活因子的表达,采用MTT试验测定卵巢癌细胞对TAM和17β-雌二醇(E2)的敏感性。结果:4种卵巢癌细胞均表达ERα,其中A2780细胞较低,CAOV-3和SKOV-3细胞较高,ES-2细胞居中;ERβ的表达情况则与ERα恰好相反;3种p160共激活因子mRNA的表达水平均以A2780细胞为最低,而ES-2、SKOV-3和CA-OV-3细胞则依次升高;4种卵巢癌细胞对TAM的敏感性不同,其中A2780细胞最敏感,CAOV-3、SKOV-3和ES-2细胞则有不同程度的耐药性,其耐药倍数分别为4.98、3.75和2.66;除SKOV-3细胞外,E2对CAOV-3、ES-2和A2780细胞均有不同程度的促增殖作用,其强度依次降低。结论:卵巢癌细胞ERβ表达水平与其对TAM的敏感性呈正相关趋势;3种p160共激活因子表达水平与卵巢癌细胞对TAM的敏感性呈负相关趋势,与ERα而非ERβ的表达水平相一致。

OBJECTIVE：To investigate the relationship between the expression of ER isoforms and p160 coactivitors in four epithelial ovarian cancer cell lines （A2780,CAOV-3,SKOV-3 and ES-2） and their sensitivity to tamoxifen （TAM） or estrogen. METHODS：RT-PCR and Western Blot analysis were performed to analyze the expression of ER isoforms and p160 coactivitors. MTT assay was carried out to examine the sensitivity to TAM and 17β-estradiol （E2） in ovarian cancer cells. RESULTS：Lower level of ERα was observed in A2780 cells,higher level was found in CAOV-3 and SKOV-3 cells,and moderate level was detected in ES-2 cells. The ERβ expression was opposite to the ERα expression. A gradual up-regulation of three p160 coactivators mRNA was detected in A2780,ES-2,SKOV-3 and CAOV-3 cells. The sensentivity to TAM in four ovarian cancer cells was different. A2780 cells were the most sensentive,whereas CAOV-3,SKOV-3 and ES-2 cells were drug-resistant,and their resistance fold was 4.98,3.75 and 2.66,respectively. E2 promoted CAOV-3,ES-2 and A2780,but not SKOV-3 cell proliferation. CONCLUSION：The expression levels of ERβ and p160 coactivators in epithelial ovarian cancer cell lines are positively and inversely associated with TAM sensitivity,respectively,and those of p160 coactivators are in agreement with the expression of ERα,but not ERβ in these cells.