Transfection with different connexin genes alters growth and differentiation of human choriocarcinoma cells

Transfection with different connexin genes alters growth and differentiation of human choriocarcinoma cells
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DOI:
10.1006/excr.1998.4332
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发表时间:
1999-02-01
影响因子:
3.7
通讯作者:
Winterhager, E
Winterhager, E
中科院分区:
医学3区
文献类型:
--
作者:
Hellmann, P;Grümmer, R;Winterhager, E

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为了研究通过间隙连接的细胞间通讯在控制增殖和分化中的作用,我们分别用连接蛋白26、连接蛋白40和连接蛋白43转染恶性滋养层细胞系Jeg-3,其表现出由内源性表达的连接蛋白40介导的极低的细胞间通讯。与对照相比,转染连接蛋白基因的所有细胞克隆的体外生长显著降低。这种效应对应于所有克隆的总连接电导的显着增加。由转染的连接蛋白形成的通道的单通道电导在先前公布的值的范围内。虽然总连接电导在克隆之间甚至在一个克隆内变化很大,但由β-hCG分泌指示的细胞分化在揭示最大量的良好偶联细胞对的克隆中是最突出的。连接蛋白26通道使一个克隆的细胞能够显著降低生长速率并产生显著更高的β-hCG分泌。Connexin 43对Jeg-3细胞的分化特性只有中等程度的影响。这些发现表明,细胞间通讯的恢复在肿瘤细胞的生长减少和分化中起作用,并且不同的通道蛋白可能具有不同的作用,(C)1999 Academic Press.
To examine the role of cell-cell communication via gap junctions in controlling proliferation and differentiation we transfected the malignant trophoblast cell line Jeg-3, which exhibits extremely low cell-cell communication mediated by endogenously expressed connexin40, with connexin26, connexin40, and connexin43, respectively. In vitro growth of all cell clones transfected with connexin genes was significantly reduced compared to controls. This effect corresponded to a significant increase in total junctional conductance of all clones. Single-channel conductances for channels formed by the transfected connexins were in the range of the values published previously. Though total junctional conductance varied highly among clones and even within one clone, differentiation of the cells indicated by beta-hCG secretion was most prominent in the clones that revealed the largest amount of well-coupled cell pairs. Connexin26 channels enable cells of one clone to reduce drastically growth rate and produce significantly higher secretion of beta-hCG. Connexin43 had only moderate effects on the differentiation properties of Jeg-3 cells. These findings suggest that restoration of cell-cell communication plays a role in growth reduction and in differentiation of tumor cells and that different channel proteins might have different effects, (C) 1999 Academic Press.