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首页> 外文期刊>Molecular and Cellular Biology >Restoration of Functional Gap Junctions through Internal Ribosome Entry Site-Dependent Synthesis of Endogenous Connexins in Density-Inhibited Cancer Cells
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Restoration of Functional Gap Junctions through Internal Ribosome Entry Site-Dependent Synthesis of Endogenous Connexins in Density-Inhibited Cancer Cells

机译：通过内部核糖体进入位点依赖密度抑制癌细胞内源性连接蛋白的合成来恢复功能性缝隙连接。

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Gap junctions are composed of connexins and are critical for the maintenance of the differentiated state. Consistently, connexin expression is impaired in most cancer cells, and forced expression of connexins following cDNA transfection reverses the tumor phenotype. We have found that the restoration of density inhibition of human pancreatic cancer cells by the antiproliferative somatostatin receptor 2 (sst2) is due to overexpression of endogenous connexins Cx26 and Cx43 and consequent formation of functional gap junctions. Immunoblotting along with protein metabolic labeling and mRNA monitoring revealed that connexin expression is enhanced at the level of translation but is not sensitive to the inhibition of cap-dependent translation initiation. Furthermore, we identified a new internal ribosome entry site (IRES) in the Cx26 mRNA. The activity of Cx26 IRES and that of the previously described Cx43 IRES are enhanced in density-inhibited cells. These data indicate that the restoration of functional gap junctions is likely a critical event in the antiproliferative action of the sst2 receptor. We further suggest that the existence of IRESes in connexin mRNAs permits connexin expression in density-inhibited or differentiated cells, where cap-dependent translation is generally reduced.
机译：间隙连接由连接蛋白组成，对于维持分化状态至关重要。一致地，在大多数癌细胞中连接蛋白表达受损，并且在cDNA转染后连接蛋白的强制表达逆转了肿瘤表型。我们已经发现，抗增殖生长抑素受体2（sst2）对人胰腺癌细胞密度抑制的恢复是由于内源性连接蛋白Cx26和Cx43的过表达以及功能间隙连接的形成。免疫印迹以及蛋白质代谢标记和mRNA监测显示连接蛋白表达在翻译水平上增强，但对抑制cap依赖性翻译起始并不敏感。此外，我们在Cx26 mRNA中鉴定了一个新的内部核糖体进入位点（IRES）。 Cx26 IRES和先前描述的Cx43 IRES的活性在密度抑制细胞中得到增强。这些数据表明功能间隙连接的恢复可能是sst2受体抗增殖作用中的关键事件。我们进一步建议连接蛋白mRNA中存在IRESes允许连接蛋白在密度抑制或分化的细胞中表达，在这些细胞中，帽依赖性翻译通常会减少。

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