Negative growth control of HeLa cells by connexin genes: connexin species specificity.

Negative growth control of HeLa cells by connexin genes: connexin species specificity.
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DOI:
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发表时间:
1995-02
期刊:
影响因子:
11.2
通讯作者:
M. Mesnil;V. Krutovskikh;C. Piccoli;C. Elfgang;O. Traub;K. Willecke;H. Yamasaki
M. Mesnil;V. Krutovskikh;C. Piccoli;C. Elfgang;O. Traub;K. Willecke;H. Yamasaki
中科院分区:
医学1区
文献类型:
--
作者:
M. Mesnil;V. Krutovskikh;C. Piccoli;C. Elfgang;O. Traub;K. Willecke;H. Yamasaki

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为了检测不同的连接蛋白基因是否发挥不同程度的抑瘤活性,我们研究了缝隙连接缺陷的人癌细胞株HeLa细胞在转染三种不同连接蛋白(Cx)26、Cx 40和Cx 43的基因前后的生长特性。所有细胞系(3个CX-26、2个CX-40、1个CX-43)均显示细胞间缝隙连接通讯(GJIC)的建立。与亲代HeLa细胞相比,CX26基因转染组中的两个克隆细胞生长明显减慢。在软琼脂中生长时,CX26的3个克隆的生长明显低于其他转染体和亲本HeLa细胞。当注射到裸鼠体内时,两个转录量最高的Cx26克隆几乎不会诱发肿瘤,而其他转染体,包括转录量最低的Cx26克隆,则具有致瘤性。在不同连接蛋白基因的转染者中,其GJIC与致瘤性之间没有很好的负相关关系。克隆Cx26A和E在裸鼠体内诱导的GJIC水平显著升高。这些结果表明,所有的连接蛋白基因都能诱导HeLa细胞GJIC的恢复,但只有Cx26基因对HeLa细胞有很强的负生长控制作用,因此,该连接蛋白基因可能具有不同于其他连接蛋白基因的功能。
In order to examine whether different connexin gene species exert different degrees of tumor-suppressing activity, we characterized growth characteristics of a gap junction-deficient human cancer cell line, HeLa cells, before and after transfection with cDNA for three different connexins, connexin (cx) 26, cx 40, and cx 43. All transfected cell lines (3 clones transfected with the cx 26 gene, 2 clones with cx 40, and 1 with cx 43) showed establishment of gap junctional intercellular communication (GJIC). Two of the cx 26-transfected clones showed significantly slower growth compared with the parental HeLa cells. When transfectants were grown in soft agar, the three cx 26-transfected clones grew much less than the other transfectants and parent HeLa cells. When injected into nude mice, the two cx 26 clones which exhibited the highest amount of cx 26 transcript induced almost no tumors, whereas other transfectants, including the cx 26 clone which exhibited the lowest amount of cx 26 transcript, were tumorigenic. Among transfectants of various connexin genes, there was no good inverse correlation between their GJIC and tumorigenicity. GJIC levels were significantly higher in tumors induced in nude mice by clone cx 26 A and E transfectants. These results suggest that all of the connexin genes examined could induce recovery of GJIC of HeLa cells, but only the cx 26 gene exerts strong negative growth control on HeLa cells; thus, this connexin gene may have different functions from other connexin genes.