Mutated connexin43 proteins inhibit rat glioma cell growth suppression mediated by wild-type connexin43 in a dominant-negative manner

Int J Cancer. 1998 Nov 9;78(4):446-53. doi: 10.1002/(sici)1097-0215(19981109)78:4<446::aid-ijc10>3.0.co;2-4.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Division / genetics
  • Connexin 43 / genetics*
  • Connexin 43 / metabolism
  • Connexin 43 / physiology
  • Gap Junctions / metabolism
  • Genes, Tumor Suppressor*
  • Glioma
  • Mice
  • Mice, Nude
  • Mutagenesis, Site-Directed
  • Neoplasm Transplantation
  • Phosphorylation
  • Rats
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Connexin 43