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糖原合酶激酶3#beta#以细胞周期蛋白D1依赖性方式引发人肺腺癌细胞A549细胞周期阻滞

李建莎, 朱敏, 田丹, 王满香, 王芳, 李娜萍, 吴人亮

华中科技大学同济医学院病理学系,卫生部呼吸系统疾病重点实验室.湖北,武汉 430030

摘要

对糖原合酶激酶3#beta#(glycogen synthase kinase 3#beta#,6SK3#beta#)在细胞增殖中的作用研究,在不同细胞系和不同刺激因素作用下得出了不同结论,该文旨在探讨GSK3#beta#在人肺腺癌细胞系A549细胞生长中的直接作用。A549细胞瞬时转染持续激活型S9A--GSK3#beta#以及显性负突变型KM--GSK3#beta#两种GSK3#beta#突变型质粒,改变GSK3#beta#活性。24 h后,分别进行细胞计数,流式细胞术及Western blot检测。结果显示,增强GSK3#beta#活性可导致细胞数量下降,G_(1)期细胞百分比升高。细胞周期蛋白D1表达水平被GSK3#beta#下调。结果提示,GSK3#beta#可能以细胞周期蛋白D1依赖性方式引发A549细胞的G_(1)期阻滞,从而发挥生长抑制效应。

关键词： 糖原合酶激酶3#beta#; 细胞增殖; 细胞周期; 细胞周期蛋白D1

Glycogen synthase kinase 3#beta# induces cell cycle arrest in a cyclin D1--dependent manner in human lung adenocarcinoma cell line A549

Li Jiansha, Zhu Min, Tian Dan, Wang Manxiang, Wang Fang, Li Naping, Wu Renliang

Department of Pathology,Tongji Medical College,Huazhong University of Science and Technology,and Key Laboratory of Pulmonary Disease of Ministry of Health of China.Wuhan 430030,Hubei

Abstract

The effect of glycogen synthase kinase 3#beta# (GSK3#beta#) has been repeatedly implicated in cell proliferation, but studies on the effect of GSK3#beta# in different cell lines with different stimuli have drawn different conclusions. To investigate the direct effect of GSK3#beta# on cell growth in human lung adenocarcinoma cell line A549, we changed its activity by transient transfection with two kinds of GSK3#beta# mutant plasmids, constitutively active form S9A-GSK3#beta# and dominant negative form KM-GSK3#beta#. Twenty-four hours later, cell counting, flow cytometry and Western blot detection were made respectively. The results showed that enhancing GSK3#beta# activity caused a decrease in cell number, as well as a higher percentage of cells at G_(1) phase. Further, the expression of cyclin D1 was downregulated by GSK3#beta#. Taken together, our observations suggest that GSK3#beta# may induce G_(1) cell cycle arrest in a cyclin D1-dependent fashion and therefore possibly plays a growth-inhibitory role in A549 cells.

Key words: glycogen synthase kinase 3#beta#;Cell proliferation;Cell cycle;cyclin D1

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引用本文：

李建莎, 朱敏, 田丹, 王满香, 王芳, 李娜萍, 吴人亮. 糖原合酶激酶3#beta#以细胞周期蛋白D1依赖性方式引发人肺腺癌细胞A549细胞周期阻滞[J]. 生理学报 2007; 59 (2): 204-209.

Li Jiansha, Zhu Min, Tian Dan, Wang Manxiang, Wang Fang, Li Naping, Wu Renliang. Glycogen synthase kinase 3#beta# induces cell cycle arrest in a cyclin D1--dependent manner in human lung adenocarcinoma cell line A549. Acta Physiol Sin 2007; 59 (2): 204-209 (in Chinese with English abstract).