Incorporation of the gene for a cell-cell channel protein into transformed cells leads to normalization of growth
Incorporation of the gene for connexin 43, a cell-cell channel protein of gap junction, into the genome of communication-deficient transformed mouse 10T1/2 cells restored junctional communication and inhibited growth. Growth was slowed, saturation density reduced and focus formation suppressed, and these effects were contingent on overexpression of the exogenous gene and the consequent enhancement of communication. In coculture with normal cells the growth of the connexin overexpressors was completely arrested, as these cells established strong communication with the normal ones. Thus, in culture by themselves or in coculture, the connexin overexpressor cells grew like normal cells. These results demonstrate that the cell-cell channel is instrumental in growth control; they are the expected behavior if the channel transmits cytoplasmic growth-regulatory signals.
Key Wordsintercellular communication gap junction connexin growth control cDNA connexin43 cell-cell channel junctional communication transformation cancer etiology
Unable to display preview. Download preview PDF.
- Ausubel, F.M., Brent, R., Kingston, R.E., Moore, D.D., Seidman, J.G., Smith, J.A., Struhl, K. 1987. Current Protocols in Molecular Biology. John Wiley & Sons, New YorkGoogle Scholar
- Azarnia, R., Loewenstein, W.R. 1984. Intercellular communication and the control of growth: X. Alteration of junctional permeability by thesrc gene. A study with temperaturesensitive mutant Rous sarcoma virus.J. Membrane Biol. 82:191–205Google Scholar
- Borek, C., Higashino, S., Loewenstein, W.R. 1969. Intercellular communication and tissue growth: IV. Conductance of membrane junctions of normal and cancerous cells in culture.J. Membrane Biol. 1:274–293Google Scholar
- Loewenstein, W.R. 1979. Junctional intercellular communication and the control of growth.Biochim. Biophys. Acta Cancer Rev. 560:1–65Google Scholar
- Maldonado, P.E., Rose, B., Loewenstein, W.R. 1988. Growth factors modulate junctional cell-to-cell communication.J. Membrane Biol. 106:203–210Google Scholar
- Maniatis, T., Fritsch, E.F., Sambrook, J. 1989. Molecular Cloning: A Laboratory Manual. Vol. 1–3. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.Google Scholar
- Musil, L.S., Beyer, E.C., Goodenough, D.A. 1990a. Expression of the gap junction protein connexin43 in embryonic chick lens: Molecular cloning, ultrastructural localization, and post-translational phosphorylation.J. Membrane Biol. 116:163–175Google Scholar
- Nonner, W.F., Loewenstein, W.R. 1989. Appendix: A growth control model with discrete regulatory centers.J. Cell Biol. 108:1063–1065Google Scholar
- Rogers, M., Berestecky, J.M., Hossain, M.Z., Guo, H., Kadle, R., Nicholson, B., Bertram, J.S. 1990. Retinoid-enhanced gap junctional communication is achieved by increased levels of connexin43 mRNA and protein.Mol. Carcinogen. 3:335–343Google Scholar
- Swenson, K.I., Piwnica-Worms, H., McNamee, H., Paul, D.L. 1990. Tyrosine phosphorylation of the gap junction protein connexin 43 accounts for the pp60v-src-induced inhibition of communication inXenopus oocyte pairs.Cell Reg. 1(13):989–1002Google Scholar