Gap junctional intercellular communication and connexin expression in normal and SV 40-transformed human liver cells in vitro.
The gap junction intercellular communication (GJIC) capacity of two normal human liver-derived epithelial cell strains and their SV40 large T oncogene-transformed counterparts was examined. In homologous cultures the GJIC capacity of the transformed cells was considerably less than the parental cells. In heterologous cultures, transformed cells appeared to be able to form GJIC channels with normal cells. Only non-transformed cells expressed connexin (cx) 43 gene and cx 26 or cx 32 transcripts were not detectable in any cell strains tested. When GJIC was assayed in the presence of the phorbol ester tumour promoter 12-O-tetradecanoylphorbol-13- acetate (TPA), all four strains showed a marked sensitivity to TPA in inhibitory activity at 1-10 ng/ml. In contrast to a rat liver epithelial cell line, this effect of TPA did not appear to become refractory even after 24 h exposure. These studies demonstrate that GJIC of human liver cells in culture can be decreased by viral oncogene and tumour promoter action. Such disturbance may be an important component of the carcinogenic activity of these agents.
Public and Environmental Health Division, Adelaide, SA, Australia.
D J
DJ
Fitzgerald
S H
SH
Swierenga
M
M
Mesnil
C
C
Piccoli
N
N
Marceau
H
H
Yamasaki
D000328:Adult; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D002450:Cell Communication / Q000187:drug effects; D002472:Cell Transformation, Viral; D002478:Cells, Cultured / Q000187:drug effects; D017630:Connexins; D015870:Gene Expression; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000952:Antigens, Polyomavirus Transforming; D017630:Connexins; D008565:Membrane Proteins; D013755:Tetradecanoylphorbol Acetate