Mutated connexin43 proteins inhibit rat glioma cell growth suppression mediated by wild-type connexin43 in a dominant-negative manner.
Many lines of evidence support the hypothesis that connexins form a family of tumor-suppressor genes. Transfection of connexin43 (Cx43) into rat C6 glioma cells have revealed that Cx43 functions as a growth- and tumor-suppressor in C6 cells. In previous studies, we and others have reported that several mutant connexins can inhibit gap junctional intercellular communication (GJIC) realized by the wild type in a dominant-negative manner. We have now examined dominant-negative effects of Cx43 mutants on cell growth control exerted by wild-type Cx43 in C6 cells. When 2 Cx43 mutants (L160M and A253V) were transfected into Cx43-transfected C6 cells, they restored anchorage-independent growth capacity and reinforced the tumorigenicity of these cells, meaning that these 2 mutants can inhibit growth-suppressive function of wild-type Cx43 in a dominant-negative manner. Neither of the mutants appeared to affect phosphorylation states and subcellular localization of Cx43 proteins. Intriguingly, the mutant A253V did not suppress GJIC capacity, implying a growth-suppressive pathway mediated by Cx43 may not be related to GJIC.
Omori
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Y
Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, Lyon, France.
Yamasaki
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H
D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division / Q000235:genetics; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D017629:Gap Junctions / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D005910:Glioma; D051379:Mice; D008819:Mice, Nude; D016297:Mutagenesis, Site-Directed; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
D018031:Connexin 43