Exogenous Cx43 expression decrease cell proliferation rate in rat hepatocarcinoma cells independently of functional gap junction.

Exogenous Cx43 expression decrease cell proliferation rate in rat hepatocarcinoma cells independently of functional gap junction.
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DOI:
10.1186/1475-2867-9-22
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发表时间:
2009-08-13
影响因子:
5.8
通讯作者:
Machado-Santelli GM
Machado-Santelli GM
中科院分区:
医学2区
文献类型:
--
作者:
Ionta M;Ferreira RA;Pfister SC;Machado-Santelli GM

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间隙连接细胞间通讯(GJIC)被认为在调节稳态中发挥作用,因为它调节重要的过程,如细胞增殖和细胞分化。已经在实体瘤中观察到GJIC能力降低或丧失,并且研究已经证明肿瘤细胞中的GJIC恢复有助于转化表型的逆转。这一观察结果支持了这样一种观点,即在这一过程中,功能通道的恢复是必不可少的。然而,在过去的几年中,有报道提出,只是在特定的连接蛋白的表达增加可以有助于在一些肿瘤细胞的恶性表型的逆转。本实验研究了外源性连接蛋白43(Cx43)表达对大鼠肝癌细胞增殖行为和表型的影响。外源性Cx43并不增加转染细胞的GJIC能力,但它是至关重要的,降低细胞增殖率以及肌动蛋白丝的重组和细胞扁平化。我们还观察到Cx43转染后对底物的粘附能力更强。Cx43的表达可抑制大鼠肝癌细胞的生长,并有助于转化表型的逆转。这些作用不依赖于GJIC,可能与Cx43蛋白磷酸化模式的改变和重新分布有关。
Gap junction intercellular communication (GJIC) is considered to play a role in the regulation of homeostasis because it regulates important processes, such as cell proliferation and cell differentiation. A reduced or lost GJIC capacity has been observed in solid tumors and studies have demonstrated that GJIC restoration in tumor cells contribute to reversion of the transformed phenotype. This observation supports the idea that restoration of the functional channel is essential in this process. However, in the last years, reports have proposed that just the increase in the expression of specific connexins can contribute to reversion of the malign phenotype in some tumor cells. In the present work, we studied the effects of exogenous Connexin 43 (Cx43) expression on the proliferative behavior and phenotype of rat hepatocarcinoma cells. The exogenous Cx43 did not increase GJIC capacity of transfected cells, but it was critical to decrease the cell proliferation rate as well as reorganization of the actin filaments and cell flattening. We also observed more adhesion capacity to substrate after Cx43 transfection. Cx43 expression leads to a decrease of the growth of the rat hepatocellular carcinoma cells and it contributes to the reversion of the transformed phenotype. These effects were independent of the GJIC and were probably associated with the phosphorylation pattern changes and redistribution of the Cx43 protein.
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