雌激素通过MTO1/HSP10轴对乳腺癌细胞增殖的影响

Estrogen promotes breast cancer cell proliferation through MTO1/HSP10 axis

目的探讨雌激素通过调控MTO1/HSP10对乳腺癌MCF-7细胞增殖与转移的影响。方法选取中国医科大学北京顺义医院收治的20例乳腺癌患者作为研究对象,检测患者乳腺癌组织和癌旁组织中MTO1和HSP10 mRNA的表达;使用不同浓度(0.05、0.10、0.15、0.20μg/ml)雌激素干预,采用CCK-8法检测各组细胞增殖,采用Western blot检测MTO1和HSP10蛋白表达,采用Transwell法检测各组细胞的迁移能力。结果中剂量雌激素组的细胞72 h增殖(2.11±0.19)和迁移能力(35.17±3.46)明显高于低剂量组[(1.24±0.09)(19.38±2.01)(P<0.05)];次高剂量组细胞72 h增殖(3.04±0.21)和迁移能力(54.18±4.36)显著高于中剂量组(P<0.05);乳腺癌中组织的MTO1相对表达量明显低于癌旁组织(P=0.003),乳腺癌组织中HSP10相对表达量明显高于癌旁组织(P=0.005);与MTO1空载组(3.76±0.19)相比,MTO1过表达组(1.58±0.09)和MTO1过表达+HSP10过表达NC组(1.65±0.11)72 h细胞增殖能力明显降低(P=0.001、0.004),与MTO1过表达组相比,MTO1过表达+HSP10过表达组(2.87±0.15)中的72 h细胞增殖能力则有所增高(P=0.011)。结论过表达雌激素可抑制MTO1蛋白的表达,促进HSP蛋白表达,MTO1通过下调HSP10表达抑制乳腺癌细胞增殖。

Objective To investigate the effect of estrogen on proliferation and metastasis of breast cancer MCF-7 cells by regulating MTO1/HSP10.Methods 20 patients with breast cancer admitted to Shunyi Hospital of China Medical University were selected as the research objects.The expressions of MTO1 and HSP10 mRNA in breast cancer tissues and adjacent tissues were detected.Different concentrations of estrogen were used to intervene(0.05μg/ml,0.10μg/ml,0.15μg/ml,0.20μg/ml).The cell proliferation was detected by CCK-8 method,the expression of MOT1 and HSP10 protein was detected by Western blot,and the migration ability of each group was detected by Transwell method.Results The cell proliferation and migration ability of the medium dose group[(2.11±0.19)(35.17±3.46)]was significantly higher than that of the low dose group[(1.24±0.09)(19.38±2.01)]at 72h(P<0.05),and the cell proliferation and migration ability of the sub high dose group[(3.04±0.21)(54.18±4.36)]was significantly higher than that of the medium dose group at 72 h(P<0.05)The relative expression of MTO1 in breast cancer tissue was significantly lower than that in adjacent tissue(P=0.003),and the relative expression of HSP10 in breast cancer tissue was significantly higher than that in adjacent tissue(P=0.005);Compared with MTO1 empty group(3.76±0.19),the proliferation ability of MTO1 overexpression group(1.58±0.09)and MTO1 overexpression+HSP10 overexpression NC group(1.65±0.11)were significantly decreased at 72 h(P=0.001,0.004),and the cell proliferation ability of MTO1 overexpression+HSP10 overexpression group(2.87±0.15)was higher than that of MTO1 overexpression group at 72h(P=0.011).Conclusions Overexpression of estrogen can inhibit the expression of MTO1 protein and promote the expression of HSP protein.MTO1 inhibits breast cancer cell proliferation by down-regulating the expression of HSP10.