This work was supported by grants from The National Natural Sciences Foundation of China (30000083) , Science and Technology Bureau of Shanghai Municipal Government (00JC 14042) and The Key Laboratory of Molecular Medicine, Ministry of Education, China.
E-cadherin-negative human breast carcinoma cell lines, MDA-MB-231 and MDA-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 β-catenin, the cyclin D1 gene transcriptional regulator. At the meantime, PKB protein level, which can inhibit β-catenin destruction through GSK-3β, 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, β-catenin and cyclin D1 protein level increased and more cells were retarded in G0/G1 phase.
WU Heng, SHEN Min-Xiong, LIANG Yu-Long, DUAN Ling-Ling, WANG Li-Ying, XU Zhen, ZHA Xi-Liang. Positive Expression of E-cadherin Retards More Human Breast Carcinoma Cells in G0/G1 Phase and its Molecular Mechanism[J]. Progress in Biochemistry and Biophysics,2003,30(3):435-441
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