Cx32 gene mutation in a chemically induced rat liver tumour.
Cx32 is a major gap junction protein of the liver and is often aberrantly expressed in liver tumours. We have studied mutation of the Cx32 gene during chemically induced hepatocarcinogenesis. DNA from 12 rat liver tumours induced by diethylnitrosamine or N-ethyl-N-hydroxyethylnitrosamine (EHEN) was analysed by the PCR/SSCP method. One tumour induced by EHEN harboured a G--> A transition mutation at codon 220, substituting His for Arg. When the mutant DNA was transfected into HeLa cells, which are deficient in gap junctional intercellular communication (GJIC), GJIC recovered, as in HeLa cells transfected with the wild-type Cx32 gene. Moreover, GJIC was modulated by cAMP, 12-O-tetradecanoylphorbol-13-acetate and lysophosphatidic acid similarly in mutant and wild-type Cx32 transfectants. These results suggest that Cx32 gene mutations are rarely involved in rat hepatocarcinogenesis and that the mutation found in a tumour may be functionally silent.
Omori
Y
Y
Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, Lyon, France.
Krutovskikh
V
V
Mironov
N
N
Tsuda
H
H
Yamasaki
H
H
D000236:Adenoma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D017630:Connexins / Q000096:biosynthesis / Q000235:genetics*; D004052:Diethylnitrosamine / Q000031:analogs & derivatives* / Q000633:toxicity*; D005091:Exons; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D007438:Introns; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D000097002:Gap Junction beta-1 Protein
D002273:Carcinogens; D017630:Connexins; D004052:Diethylnitrosamine; D011994:Recombinant Proteins; D000097002:Gap Junction beta-1 Protein; C023845:N-ethyl-N-hydroxyethylnitrosamine