外源性17β-雌二醇促进HER2阳性乳腺癌细胞的侵袭和增殖

Exogenous 17β-estradiol promote the invasion and proliferation of HER2 positive breast cancer cells

目的:研究外源性雌激素是否对乳腺癌中人表皮生长因子受体2(HER2)阳性乳腺癌细胞产生作用。方法:分别以乳腺癌细胞SKBR3和MCF-7为材料,选择17β-雌二醇(E2)为外源雌激素,配制10^(-5)、10^(-6)、10^(-7)、10^(-8)、10^(-9)、10^(-10) mol/L的6种浓度培养环境,每种浓度培养时间设置24、48、72 h 3个梯度。检测HER2、ERα等标志物表达水平变化,分析E2对HER2阳性乳腺癌细胞增殖能力及侵袭性的影响。结果:在MCF-7中处理组HER2、ERα的转录水平都明显高于阴性对照组。在SKBR3细胞中仅HER2转录水平明显高于阴性对照组(P<0.05)。在蛋白水平SKBR3中HER2蛋白表达量增加(P<0.05);而在MCF-7中,ERα蛋白表达量随着时间的延长而增加,HER2几乎检测不到。在细胞增殖方面,MCF-7和SKBR3均随着E2浓度的上升细胞增殖率上升,差异有统计学意义(P<0.05)。而在侵袭性方面,MCF-7的侵袭性在72 h时较空白对照组增强(P<0.05),SKBR3侵袭性在24 h和48 h时较空白对照组增强(P<0.05),但是自身随浓度变化的规律不明显。结论:外源性雌激素对HER2阳性乳腺癌细胞的侵袭和增殖有促进作用。

Objective： To investigate the correlation between exogenous estrogens （EEs） and the devel-opment risk of HER2 positive breast cancer cells. Methods： We treated HER2-positive and ERα-negative cells SKBR3, ERα-positive and HER2-negative cells MCF-7 with 17β-estradiol. The six different concentra-tions of 17β-estradiol were 10-5, 10-6, 10-7, 10-8, 10-9, 10-10 mol/L. For each concentration condition, there were three time dose such as 24 h, 48 h, 72 h. The expression levels of HER2 and ERα were observed as the key positive marker. And then cell invasion and cell proliferation of breast cancer cells were analysed for MCF-7 and SKBR3 under 17β-estradiol treatment. Results： It showed that the transcriptional levels of HER2 and ERα were upregulated in MCF7 cells under all 18 different conditions. However, only the transcriptional levels of HER2 was upregulated in all 18 different conditions in HER2-positive and ERα-negative SKBR3. At protein expression levels, HER2 in SKBR3 cells and ERα in MCF-7 cells were expressed apparently after the breast cancer cells were stimulated by 17β-estradiol under all different conditions. Simultaneously,the prolif-eration of MCF-7 and SKBR3 were promoted obviously. With the higher concentration of 17β-estradiol treat-ment the proliferative activity of these two breast cancer cells were promoted much more obviously. As for the invasion of the breast cancer cells, MCF-7 was increased after 72 h, and SKBR3 was increased after 24 h and 48 h. Whereas the invasion of SKBR3 and MCF-7 were not up or down regulated evidently with the changeof concentrations and time. Conclusion： In a word, the expression levels of HER2 in HER2 positive breastcancer cells SKBR3 are upregulated under different 17β-estradiol treatment conditions. Furthermore, the inva-sion and proliferation of HER2 positive breast cancer cells SKBR3 are promoted under exogenous estrogens 17β-estradiol treatment.