Chemical, oncogene and growth factor inhibition gap junctional intercellular communication: an integrative hypothesis of carcinogenesis.
Most, if not all, cancer cells have some dysfunction in gap-junction-mediated intercellular communication, either because of defects in cell adhesion or inability to have functional gap junctional communication. In addition, most, if not all, tumor-promoting chemicals and conditions down-regulate gap junction function, while some antitumor-promoting chemicals can up-regulate gap junctional communication. Several oncogenes are associated with down-regulation of gap junction function and several hormone and growth regulators, known to be tumor promoters, are also able to down-regulate gap junction function. On the other hand, some tumor suppressor genes have been linked to the up-regulation of gap junctions. Based on these observations, it is hypothesized that, if a progenitor cell is unable to perform gap junctional intercellular communication, normal growth control and cell differentiation would not be possible, thereby favoring the development of malignant neoplasia.
Trosko
J E
JE
Department of Pediatrics/Human Development, College of Human Medicine, Michigan State University, East Lansing.
Chang
C C
CC
Madhukar
B V
BV
Klaunig
J E
JE
D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects* / Q000502:physiology; D009369:Neoplasms / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D009374:Neoplasms, Experimental / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D009857:Oncogenes / Q000502:physiology*
D006133:Growth Substances