我们还应设想Cx除调控细胞间通讯外的其它功能及相关影响因素。研究发现人神经胶质瘤细胞的正常化与转染Cx43基因的胞浆正确定位有关而与GJIC功能的上调无明显关系[33]。de Feijter等[34]研究发现对大鼠肝细胞转染癌基因后Cx43异常定位于细胞核内。这是否提示一种可能，Cx与某种启动信息向胞核内传递的信号途径有关？现已发现某些Cx分子的确能够直接与多种蛋白分子互相作用。例如Cx43基因中有一个调控位点，可以与ZO-1蛋白的第二个PDZ结构域结合并相互作用[35]。目前对这种作用的意义尚不清楚，但随着研究的深入，有可能发现更多的调控蛋白，如果其中某些与细胞信号上传至细胞核相关，就可以解释Cx过表达导致细胞表型正常化的特异性基因改变的机制和正常信息分子的来源问题。

　　西安大略大学研究小组Zhu D等发现了几种神经胶质瘤细胞自分泌的与GJID功能及细胞生长有关的生长因子，包括胰岛素样生长因子IGF-1及其结合蛋白IGFBP-3、Ca2+离子等，他们认为是Cx43基因的转染和过表达刺激细胞分泌某种生长抑制因子，该因子影响了GJIC功能，使细胞生长抑制。

　　现大部分学者认为肿瘤中Cx和GJIC的缺陷是一种肿瘤的遗传变异，已将Cx基因家族视为第二类抑癌基因，即区别于经典的由于DNA的突变或缺失导致功能丧失的一类抑癌基因，它属于非突变型抑癌基因，是由于调节性的表达受阻而导致功能丧失的基因。这类基因被猜测由另外一种抑制基因所调节，后者因基因突变或缺失而致自身功能丧失[36]。

　　5结语

　　Cx家族基因及分子与多种细胞的表型转化和肿瘤的发生及演进密切相关，Cx基因的表达对绝大多数肿瘤细胞的生长起负调控作用，GJIC功能恢复后表现出对细胞恶性转化表型的逆转和肿瘤生长的抑制。但是，有关Cx与肿瘤之间的因果关系及作用机制相当复杂，研究的深入令其更加扑朔迷离。如果能够彻底揭示这些奥秘，将对我们抗癌研究作出巨大贡献。

　　有意义的是，Cx的表达可受多种内源性或外源性因素的影响，这为我们进行Cx与肿瘤、Cx与抗肿瘤药物作用机制关系的研究提供了方便，为揭示肿瘤生物学行为的分子机制及临床开发抗癌新药提供了新方向。另外，它还改变了传统肿瘤治疗中单一追求彻底杀死瘤细胞的指导思想，丰富和完善了抗肿瘤理论。寻找有效药物诱导和调控Cx基因的表达、恢复由它介导的GJIC功能将成为肿瘤化疗和基因治疗的新理念。

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