ABSTRACT

This chapter reviews the current knowledge of structure, function, regulation and study methods of gap junctional intercellular communication (GJIC), as well as the role of GJIC disorders in carcinogenesis with particular regard to its possible application for carcinogen identification and characterization. One such nonmutagenic mechanism of carcinogenesis that is supported by abundant experimental evidence is the inhibition of GJIC. The idea to develop a short-term screening test to detect or predict carcinogenicity based upon inhibition of GJIC was formed when it was found that tumor promoters could specifically impair intercellular communication in cell culture. Besides a vast and vaguely defined role of GJIC in tissue homeostasis, several other specific physiological roles have been postulated for GJIC. Genetic alteration of GJIC may occur at the initiation stage of carcinogenesis, when genotoxic carcinogens induce mutations in connexin genes or other genes related to cell-cell interaction machinery. Apparently different connexins are playing differing roles in growth regulation and tumor suppression.