Reduction of malignant phenotype of HEPG2 cell is associated with the expression of connexin 26 but not connexin 32
Reduction of malignant phenotype of HEPG2 cell is associated with the expression of connexin 26 but not connexin 32
复制标题
DOI：
10.1093/carcin/22.10.1593
复制
发表时间：
2001-10-01
期刊：
影响因子：
4.7
通讯作者：
Yamasaki, H
中科院分区：
文献类型：
--
作者：
Yano, T;Hernandez-Blazquez, FJ;Yamasaki, H
连接蛋白（Connexin, Cx）基因对肿瘤细胞具有一定的特异性负生长作用。然而，目前尚不清楚是否每个Cx基因在生长控制中都有相似的作用。肝细胞通常表达Cx26和Cx32作为其主要的间隙连接基因，但肝癌细胞系HepG2细胞由于Cx26的下调和Cx32的异常定位而缺乏间隙连接细胞间通讯（GJIC）。在本研究中，我们发现HepG2细胞中部分表达的Cx26蛋白定位于质膜并有助于GJIC的恢复，而Cx32蛋白仍定位于细胞质中。与模拟转染的克隆相比，转染cx26的克隆在体内和体外的生长速度明显减慢，并且不依赖于锚定的生长能力降低。由于E-cadherin细胞粘附复合体的重建，转染cx26的细胞具有更规则的细胞层。转染Cx26后诱导E-cadherin表达。Cx26的表达同时将E-cadherin和β -catenin蛋白带入质膜，而β -catenin蛋白的表达水平未发生变化。这些结果表明，Cx26的表达通过诱导E-cadherin和随后形成细胞粘附复合物，参与了HepG2细胞的负生长控制和形态学改变。
Connexin (Cx) genes have a negative growth effect on tumour cells with certain specificity. However, it is not clear whether each Cx gene can act similarly in growth control. Hepatocytes normally express Cx26 and Cx32 as their major gap junction genes, but HepG2 cells, a hepatoma cell line, are deficient in gap junctional intercellular communication (GJIC) based on the down-regulation of Cx26 and aberrant localization of Cx32. In this study, we showed that some of the expressed Cx26 protein in HepG2 cells localized in the plasma membrane and contributed to recovery of GJIC, while the Cx32 protein remained localized in the cytoplasm. The Cx26-transfected clones showed a significantly slower growth in vivo as well as in vitro and reduced anchorage-independent growth ability compared with a mock-transfected clone. Cx26-transfected cells had more regular cell layers due to the re-establishment of the E-cadherin cell adhesion complex. E-cadherin expression following Cx26 transfection was induced. Cx26 expression simultaneously brought E-cadherin and beta -catenin proteins into the plasma membrane without any change in the expression level of beta -catenin protein. These results suggest that the expression of Cx26 contributes to negative growth control of HepG2 cells and the morphological change through the induction of E-cadherin and subsequent formation of cell adhesion complex.