Alterations in intercellular communication during the stage of promotion.
The promotion stage is a crucial step in the process of carcinogenesis. During this stage, the initiated cell population is clonally expanded to morphologically discriminable forms. Exogenous or endogenous agents that influence this clonal expansion have tumor-promoting activity. Inhibition of gap junctional intercellular communication is one of a number of cellular changes seen in cells after exposure to promoting agents. GJIC can be inhibited through either modification of intracellular control mechanism or through transcriptional or translational down-expression of the gap junction protein. Through either mechanism, the net effect is a decrease in GJIC by tumor promoters. This decrease in GJIC, while occurring in normal cells and preneoplastic cells alike, appears to be more efficacious in the preneoplastic cells, and appears to prevent GJIC between the preneoplastic cells and the normal surrounding hepatocytes. This isolation of the preneoplastic cells by hepatic tumor promoters from the normal surrounding hepatocytes may separate the preneoplastic cells from growth regulatory control of the normal liver, thus allowing the preneoplastic cells to clonally expand by cell proliferation. Whether the disruption of GJIC and down-regulation of gap junction protein expression seen in hepatic foci by exposure to tumor promoters are causes or effects of the resulting cell proliferation remains to be determined. Certainly, the modification of GJIC and the expression of the gap junction protein by tumor promoters are important cellular changes that produce a phenotypically altered population of hepatocytes.
Klaunig
J E
JE
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202.
D000818:Animals; D002273:Carcinogens; D002450:Cell Communication; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology; D008114:Liver Neoplasms, Experimental / Q000209:etiology*; D011230:Precancerous Conditions / Q000209:etiology
D002273:Carcinogens