The tumor promoter 12-O-tetradecanoylphorbol-13-acetate and the ras oncogene modulate expression and phosphorylation of gap junction proteins.
Open Access
- 1 October 1991
- journal article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 11 (10) , 5364-5371
- https://doi.org/10.1128/mcb.11.10.5364
Abstract
Gap junctional intercellular communication is inhibited in response to tumor promoters and oncogene transformation, suggesting that loss of this function is an important step in tumor formation. To elucidate the molecular mechanisms responsible for this inhibition, we examined the expression of gap junction proteins and mRNA in mouse primary keratinocytes after treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and/or ras transformation. During normal cell growth, keratinocytes expression the alpha 1 (connexin 43) and beta 2 (connexin 26) proteins. Within 5 min of TPA treatment, the alpha 1 protein became rapidly phosphorylated on serine residues and its expression was dramatically reduced by 24 h. The beta 2 protein, after an initial increase in expression, was also significantly reduced 24 h after treatment with TPA. ras transformation caused changes similar to those induced by TPA. The alpha 1 protein underwent an increase in serine phosphorylation, although its expression declined only slightly, while beta 2 expression was greatly reduced. The effects of TPA and ras on alpha 1 expression were additive; treatment of ras-transformed cells with TPA resulted in increased alpha 1 phosphorylation, with greatly decreased protein levels, much lower than those generated by either agent alone. These data provide a likely explanation for the similar and synergistic inhibition of gap junctional intercellular communication by phorbol esters and ras.Keywords
This publication has 50 references indexed in Scilit:
- Scrape-loading and dye transfer: A rapid and simple technique to study gap junctional intercellular communicationPublished by Elsevier ,2004
- Expression of the gap junction protein connexin43 in embryonic chick lens: Molecular cloning, ultrastructural localization, and post-translational phosphorylationThe Journal of Membrane Biology, 1990
- The v‐ras oncogene inhibits the expression of differentiation markers and facilitates expression of cytokeratins 8 and 18 in mouse keratinocytesMolecular Carcinogenesis, 1990
- Inhibition of electrical coupling in pairs of murine pancreatic acinar cells by OAG and isolated protein kinase CThe Journal of Membrane Biology, 1989
- Specific viral oncogenes cause differential effects on cell‐to‐cell communication, relevant to the suppression of the transformed phenotype by normal cellsMolecular Carcinogenesis, 1988
- An activated Harvey ras oncogene produces benign tumours on mouse epidermal tissueNature, 1986
- Reduced number of gap junctions in rat hepatocarcinomas detected by monoclonal antibodyCarcinogenesis: Integrative Cancer Research, 1986
- Transformation of Epidermal Cells in CultureJournal of Investigative Dermatology, 1983
- Tumor promoters inhibit metabolic cooperation in cocultures of epidermal and 3T3 cellsBiochemical and Biophysical Research Communications, 1979
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970