Differential changes in expression of gap junction proteins connexin 26 and 32 during hepatocarcinogenesis in rats

We examined expressions of the gap junction proteins, connexin 26 (Cx26) and 32 (Cx32), in preneoplastic and neoplastic lesions during rat hepatocarcinogenesis. A marked reduction in the number of Cx32-positive gap junctions was observed in 17% of the glutathione S-transferase placental form-positive foci, whereas 44% of the foci showed increased expression of Cx26. Most hyperplastic nodules exhibited decreased expression of Cx32, whereas 16% of the nodules showed increased expression of Cx26. In hepatocellular carcinomas, expressions of both Cx32 and Cx26 were significantly reduced. These results suggest that the expressions of Cx32 and 26 are differentially regulated during hepatocarcinogenesis, and that the decrease in Cx32 expression occurs earlier, whereas reduction in Cx26 expression occurs later in association with promotion and progression of carcinogenesis.