A quantitative inverse relationship between connexin32 expression and cell proliferation in a rat hepatoma cell line.
Gap junctions comprised of connexin proteins are involved in direct intercellular communication and the regulation of cell behaviour and homeostasis. Reduced connexin expression and loss of gap junction function is a characteristic of many cancer cells and of the effect of many non-genotoxic carcinogens that induce cell proliferation. Moreover, when certain cancer cell lines are transfected with specific connexin genes, cells can regain control over proliferation. We have employed RNA interference and dexamethasone to modulate connexin32 expression in MH(1)C(1) cells to a range of concentrations. This allowed the determination of the quantitative relationship between connexin32 protein expression and cell proliferation. The magnitude of cell proliferation, measured by bromodeoxyuridine incorporation, was inversely proportional to the level of connexin32 expression. Q-PCR indicated a lack of change of expression of a range of cell cycle-related genes at 24h. The inverse relationship between Cx32 expression and proliferation was continuous, and a threshold level of reduction of connexin32 was not observable for an influence on proliferation.
Edwards
Gareth Owain
GO
Molecular Pathobiology, School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
Jondhale
Shrikant
S
Chen
Tao
T
Chipman
J Kevin
JK
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D018816:Genes, cdc; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D051381:Rats; D016196:S Phase; D014404:Tubulin / Q000378:metabolism; D000097002:Gap Junction beta-1 Protein
D001973:Bromodeoxyuridine; D017630:Connexins; D003907:Dexamethasone; D014404:Tubulin; D000097002:Gap Junction beta-1 Protein