A quantitative inverse relationship between connexin32 expression and cell proliferation in a rat hepatoma cell line

A quantitative inverse relationship between connexin32 expression and cell proliferation in a rat hepatoma cell line
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DOI:
10.1016/j.tox.2008.08.010
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发表时间:
2008-11-20
期刊:
影响因子:
4.5
通讯作者:
Chipman, J. Kevin
Chipman, J. Kevin
中科院分区:
医学3区
文献类型:
--
作者:
Edwards, Gareth Owain;Jondhale, Shrikant;Chipman, J. Kevin

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由连接蛋白组成的间隙连接参与了细胞间的直接通讯以及细胞行为和体内平衡的调节。连接蛋白表达减少和间隙连接功能丧失是许多癌细胞的特征,也是许多非基因毒性致癌物诱导细胞增殖的作用。此外,当某些癌细胞系被特定的连接蛋白基因转染时,细胞可以重新获得对增殖的控制。我们使用RNA干扰和地塞米松将MH1C1细胞中的connexin32表达调节到一定浓度。这样就可以确定connexin32蛋白表达与细胞增殖之间的定量关系。用溴脱氧尿苷掺入法测定的细胞增殖程度与connexin32的表达水平成反比。Q-PCR结果显示,在24 h时,一系列细胞周期相关基因的表达没有变化。Cx32的表达与增殖呈持续的负相关关系,connexin32的降低没有达到影响增殖的阈值水平。2008爱思唯尔爱尔兰有限公司版权所有。
Gap junctions comprised of connexin proteins are involved in direct intercellular communication and the regulation of cell behaviour and homeostasis. Reduced connexin expression and loss of gap junction function is a characteristic of many cancer cells and of the effect of many non-genotoxic carcinogens that induce cell proliferation. Moreover, when certain cancer cell lines are transfected with specific connexin genes, cells can regain control over proliferation. We have employed RNA interference and dexamethasone to modulate connexin32 expression in MH1C1 cells to a range of concentrations. This allowed the determination of the quantitative relationship between connexin32 Protein expression and cell proliferation. The magnitude of cell proliferation, measured by bromodeoxyuridine incorporation, was inversely proportional to the level of connexin32 expression. Q-PCR indicated a lack of change of expression of a range of cell cycle-related genes at 24 h. The inverse relationship between Cx32 expression and proliferation was continuous, and a threshold level of reduction of connexin32 was not observable for an influence on proliferation. (c) 2008 Elsevier Ireland Ltd. All rights reserved.