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首页> 外文期刊>Life sciences >Connexin 32 down-regulates the fibrinolytic factors in metastatic renal cell carcinoma cells.
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Connexin 32 down-regulates the fibrinolytic factors in metastatic renal cell carcinoma cells.

机译：连接蛋白32下调转移性肾细胞癌细胞中的纤溶因子。

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摘要

Fibrinolytic factors have an important role in tumor progression through the degradation of extracellular matrix. The increased levels of urokinase-type plasminogen activator (uPA), uPA-receptor (uPAR) and type-1 PA inhibitor (PAI-1) are reported in human renal cell carcinoma (RCC). Connexin (Cx) gene, a member of gap junction, is known to act as a tumor suppressor gene. We have reported that Cx32 improves malignant phenotypes of metastatic RCC cells via the inhibition of Src-dependent signaling. In this study, we examined the effect of expression of Cx32 gene on the production of uPA, uPAR and PAI-1, and on the induction of PAI-1 stimulated by hypoxia in a human metastatic RCC cell line, Caki-1 cells. Cx32 expression decreased both mRNA level and production of PAI-1, uPA and uPAR in Caki-1 cells. Cx32 also decreased hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha mRNA level. PP1, a Src inhibitor, significantly decreased PAI-1, uPA, uPAR and HIF-alpha mRNA levels in Caki-1 cells. Furthermore, Cx32suppressed the induction of HIF-2alpha protein in Caki-1 cells under hypoxia. PAI-1 mRNA level in Cx32-transfected Caki-1 cells was lower than that of mock transfectant under hypoxic conditions. These results suggest that Cx32 might reduce PAI-1, uPA and uPAR production in metastatic RCC cells via the inhibition of Src-dependent induction of HIF-1alpha and HIF-2alpha gene expression and that Cx32 might suppress hypoxia-inducible gene expression under hypoxic conditions.
机译：纤溶因子通过细胞外基质的降解在肿瘤进展中具有重要作用。据报道，在人类肾细胞癌（RCC）中，尿激酶型纤溶酶原激活剂（uPA），uPA受体（uPAR）和1型PA抑制剂（PAI-1）的水平升高。连接蛋白（Cx）基因，缝隙连接的成员，已知作为抑癌基因。我们已经报道，Cx32通过抑制Src依赖性信号传导改善了转移性RCC细胞的恶性表型。在这项研究中，我们检查了Cx32基因表达对uPA，uPA​​R和PAI-1产生以及在人转移性RCC细胞系Caki-1细胞中由缺氧刺激的PAI-1诱导的影响。 Cx32表达降低了Caki-1细胞的mRNA水平以及PAI-1，uPA和uPAR的产生。 Cx32还降低了缺氧诱导因子（HIF）-1alpha和HIF-2alpha mRNA水平。 PP1是一种Src抑制剂，可显着降低Caki-1细胞中的PAI-1，uPA，uPA​​R和HIF-alpha mRNA水平。此外，Cx32抑制缺氧下Caki-1细胞中HIF-2alpha蛋白的诱导。在缺氧条件下，Cx32转染的Caki-1细胞中PAI-1 mRNA的水平低于模拟转染子。这些结果表明，Cx32可能通过抑制Src依赖性诱导的HIF-1alpha和HIF-2alpha基因表达而减少转移性RCC细胞中PAI-1，uPA和uPAR的产生，并且Cx32可能抑制低氧条件下的低氧诱导基因表达。 。

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