摘要
表皮钙粘蛋白 (E cadherin)阴性的乳腺癌细胞株MDA MB 2 3 1和MDA MB 43 5转染野生型表皮钙粘蛋白基因 ,通过流式细胞仪测量细胞周期发现表皮钙粘蛋白阳性细胞生长变慢 ,更多细胞停滞在G0 /G1期 ,蛋白质印迹证实由G0 /G1期进入S期的重要调控分子细胞周期蛋白 D1(cyclinD1)下降了 ,并发现表皮钙粘蛋白还能降低直接激活细胞周期蛋白 D1基因转录的 β 连环蛋白的蛋白质浓度 .蛋白激酶B (PKB)能通过抑制糖原合成激酶 3 β(GSK 3 β)的活性来抑制β 连环蛋白降解 ,并在乳腺癌高转移细胞株中普遍过表达 ,其表达同样受到了表皮钙粘蛋白的抑制 .并且在表皮钙粘蛋白阳性细胞中 ,作为PKB上游信号分子并能激活PKB的粘着斑激酶 (FAK)和整联蛋白相关激酶 (ILK)蛋白量也发生下降 ,能抑制PKB激活的PTEN蛋白量却增加了 .结果显示 ,表皮钙粘蛋白能通过降低乳腺癌细胞中的PKB蛋白浓度 ,并通过上游信号分子抑制PKB的激活 ,进而降低PKB对β 连环蛋白降解的抑制作用 ,导致 β 连环蛋白直接调控的靶基因细胞周期蛋白D1的表达量下降 ,引起更多的细胞停止在G0
E-cadherin-negative human breast carcinoma cell lines, NDA-NB-231 and MA-MB-435 were transfected with wild-type E-cadherin cDNA. Flow cytometry showed that E-cadherin-positive transfectants grew slower than the control cells and more cells were relayed in G0/G1 phase. Western blot showed that it was due to down-regulation of protein concentration of cyclin D1 and beta-catenin, the cyclin D1 gene transcriptional regulator. At the meantime, PKB protein level, which can inhibit beta-catenin destruction through GSK-3beta, was also down-regulated. As the PKB activators, FAK and ILK protein levels were decreased and PKB inhibitor, PTEN was increased by positive expression of E-cadherin. Therefore, E-cadherin can inhibit PKB activity by down-regulation of FAK, ILK and up-regulation of PTEN. As a result, beta-catenin and cyclin D1 protein level increased and more cells were retarded in G0/G1 phase.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2003年第3期435-441,共7页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金资助项目 ( 30 0 0 0 0 83)
上海市科委项目( 0 0JC 14 0 42 )
教育部分子医学重点实验室资助项目~~
