摘要
[目的]探究Tau蛋白磷酸化在不同浓度雌激素诱导的肝癌细胞增殖调控中的作用机制。[方法]利用Western blot检测人体肝癌组织和癌旁组织中Tau蛋白Ser396位点磷酸化水平(p-Tau Ser396)。给予不同浓度17β-雌二醇(E2)处理敲低雌激素受体(estrogen receptor,ER)-α36的人肝癌细胞(HepG2/Si36和Huh7/Si36)和转染空载体的人肝癌细胞(HepG2/vector和Huh7/vector),利用Western blot检测p-Tau Ser396蛋白表达情况;利用集落形成实验检测肝癌细胞增殖情况。[结果]与癌旁组织相比,人体肝细胞癌组织中p-Tau Ser396表达水平明显升高。低浓度E2(1 nmol/L)可明显增强肝癌细胞(HepG2和Huh7) p-Tau Ser396蛋白表达(1.00±0.13 vs 2.89±0.14和1.00±0.14vs 2.47±0.14,P<0.01),促进其增殖(P<0.01);而高浓度E2(10μmol/L)可降低肝癌细胞(HepG2和Huh7) p-Tau Ser396蛋白表达(1.00±0.05 vs 0.27±0.05和1.00±0.05 vs 0.30±0.05,P<0.01),抑制其增殖(P<0.01)。但在敲低ER-α36的人肝癌细胞中,不同浓度E2均未能影响p-Tau Ser396蛋白表达水平和集落形成能力(P<0.01)。[结论]人体肝细胞癌组织中p-Tau Ser396高表达。低浓度E2(1 nmol/L)可增强p-Tau Ser396蛋白表达,促进肝癌细胞增殖;而高浓度E2(10μmol/L)可降低p-Tau Ser396蛋白表达,抑制肝癌细胞增殖,这一过程受ER-α36通路调控。
[Objective]The study aimed to explore the regulatory mechanism of Tau phosphorylation in hepatocellular carcino-ma(HCC)cell proliferation induced by different concentrations of estrogen.[Method]The phosphorylated level of Tau at Ser396 site(p-Tau Ser396)was measured in the primary tumor tissues and the adjacent non-malignant tissues using West-ern blot analysis.HepG2 and Huh7 cells with the knocked-down level of ER-α36 expression were established.HepG2 and Huh7 cells with different levels of ER-α36 expression were treated with different concentrations of 17β-estrogen(E2).The expression level of p-Tau Ser396 was measured by Western blot analysis,and the proliferation of HCC cells was detected by clonogenic assays.[Result]Compared with adjacent non-malignant tissues,increased level of p-Tau Ser396 was detected in tumor specimens of HCC.Low concentration of estrogen(1nmol/L)increased expression level of p-Tau Ser396(1.00±0.13 vs 2.89±0.14 and 1.00±0.14 vs 2.47±0.14,P<0.01)of HCC cell(HepG2 and Huh7)and promoted HCC cell prolifera-tion(P<0.01),while high concentration of estrogen(10μmol/L)decreased expression level of p-Tau Ser396(1.00±0.05 vs 0.27±0.05 and 1.00±0.05 vs 0.30±0.05,P<0.01)of HCC cell(HepG2 and Huh7)and inhibited HCC cell prolifera-tion(P<0.01).ER-α36 knockdown decreased expression level of p-Tau Ser396 and inhibited cell proliferation of HCC(P<0.01).E2 failed to influence the expression level of p-Tau Ser396 and cell proliferation in HepG2/Si36 and Huh7/Si36 cells(P<0.01).[Conclusion]The level of p-Tau Ser396 is highly expressed in the primary tumor samples of HCC.The ex-pression of p-Tau Ser396 is involved in estrogen-induced proliferation of HCC cells,which is regulated by ER-α36 signa-ling.
作者
刘学敏
何欢欢
王璇
王安
胡少勃
刘钰晨
舒细记
王建枝
付政祺
LIU Xuemin;HE Huanhuan;WANG Xuan;WANG An;HU Shaobo;LIU Yuchen;SHU Xiji;WANG Jianzhi;FU Zhengqi(Department of Pathology and Pathophysiology,School of Medicine,Jianghan University,Wuhan 430056;Cancer Institute,School of Medicine,Jianghan University,Wuhan 430056;Wuhan Institute of Biomedical Sciences,School of Medicine,Jianghan University,Wuhan 430056;Hubei Key Laboratory of Cognitive and Affective Disorders,School of Medicine,Jianghan University,Wuhan 430056;Liver Transplant Cancer,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)
出处
《生物技术》
2025年第6期754-760,共7页
Biotechnology
基金
国家自然科学基金项目(81872040)
江汉大学科研专项资金项目(2021jczx-002)。
