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Junctional intercellular communication is cooperatively inhibited by oncogenes in transformation
R Azarnia1, M Mitcho, D Shalloway
1Department of Physiology and Biophysics, University of Miami School of Medicine, Florida 33101.
Abstract:
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.
Insights
The cellular src (c-src) and adenovirus E1A genes cooperate to reduce cell communication, contributing to cell transformation. This cooperative loss of communication is key to understanding oncogene complementation in cancer development.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Cellular src (c-src) and adenovirus E1A are oncogenes implicated in cell transformation.
- Junctional cell-to-cell communication is crucial for regulating cell growth and behavior.
Purpose of the Study:
- To investigate the combined effects of c-src and E1A on junctional cell-to-cell communication.
- To elucidate the role of communication loss in oncogene cooperation and cell transformation.
Main Methods:
- NIH3T3 cells were transfected with c-src and/or adenovirus E1A genes.
- Junctional permeability was quantified to assess cell-to-cell communication.
Main Results:
- Neither c-src nor E1A alone completely transformed NIH3T3 cells.
- Co-transfection with both c-src and E1A resulted in significant cell transformation.
- Both genes individually reduced junctional communication, with a synergistic decrease when combined.
Conclusions:
- The cooperative transformation by c-src and E1A is linked to a synergistic reduction in junctional cell-to-cell communication.
- Loss of junctional communication is a critical factor in the decontrol of cell growth during transformation.
- This finding provides a mechanistic explanation for the complementation of these oncogenes in carcinogenesis.