Junctional intercellular communication is cooperatively inhibited by oncogenes in transformation.

We examined the actions of the cellular src (c-src) and adenovirus E1A genes on junctional cell-to-cell communication. Neither gene causes complete transformation of NIH3T3 cells on its own, but the two do so in conjunction with one another. This cooperation goes hand in hand with summation of the actions of the two genes on junctional communication: junctional permeability is reduced when the cells are transfected with either gene; it is reduced significantly more when they are transfected with both. This cooperative loss of communication approaches the noncooperative loss induced by the viral src gene (v-src), chimeric c-src/v-src, or Tyr527-mutant c-src--genes that cause transformation on their own. This provides a rationale for the hitherto unexplained complementation of the two oncogenes in carcinogenesis; it is the expected behavior if the loss of communication is causal in the decontrol of growth in transformation.