Changes in gap junction protein (connexin 32) gene expression during rat liver carcinogenesis

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Abstract
A rat liver gap junction (GJ) cDNA probe that detects mRNA encoding the 32 Kd GJ‐protein (connexin 32) was employed to study GJ‐protein gene expression in rat liver tumors induced by a single exposure to diethylnitrosamine (DEN) followed by exposure to 2‐acetylaminofluorene (AAF)/CCL4/AAF or induced by systemic administration of N‐ethyl‐N‐hydroxyethylnitrosamine (EHEN). All carcinomas generated by these carcinogens showed markedly reduced levels of GJ‐protein mRNA. This may indicate that GJ‐protein levels and gap‐junctional intercellular communication (GJIC) capacity are also severely compromised. Moreover, all hyperplastic nodules also showed a reduced level of GJ‐protein mRNA. Taken together with our earlier finding that the liver tumor promoter phenobarbital inhibits GJ‐protein gene expression, these results suggest that deranged GJIC is a relatively early event in liver multistage carcinogenesis. A range of other cDNA probes was also used to characterize gene expression in the DEN‐induced tumors. Induction of expression was seen for glutathione S‐transferase (placental form) (GST‐P), γ‐glutamyltranspeptidase (GGT), and c‐raf but not for c‐Ha‐ras or c‐myc.