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SHORT COMMUNICATION: Inhibition of gap junctional intercellular communication and delocalization of the cell adhesion molecule E-cadherin by tumor promoters
1Department of Product Quality and Safety, Agrotechnological Research Institute (ATO-DLO) PO Box 17. 6700 AA Wagenmgen
2Department of Toxicology, Agricultural University Wagenmgen Tuinlaan 5, 6703 HE Wageningen, The Netherlands
3Unit of Multistage Carcinogenesis. International Agency for Research on Cancer 150 Cours Albert-Thomas, 69372 Lyon 08, France
4Department of Food Physics and Dairy, Agricultural University Wageningen Bomenweg 2, 6703 HD Wageningen, The Netherlands
5To whom correspondence should be addressed at: ATO-DLO, PO Box 17, 6700 AA Wageningen, The Netherlands
The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) and benzoyl peroxide (BoP) on gap junctional intercellular communication (GJIC) and the amount and localization of E-cadherin was studied in initiated mouse epidermal cells (3PC) and in carcinoma cells (CA3/7) originating from the same cell type. In addition, the localization and phos-phorylation of connexin43 was studied in both cell lines and in primary keratinocytes. GJIC inhibition by TPA and BoP was stronger in primary keratinocytes compared with both cell lines. BoP strongly decreased the amount of E-cadherin protein and the level occurring in the membranes in both cell lines, whereas TPA caused a transloca-tion of E-cadherin from the membrane towards the cytosol, without decreasing the total amount of E-cadherin present. The effect of both tumor promoters on connexin43 phos-phorylation and localization was agent as well as cell dependent. These results show for the first time that tumor promoters can decrease the quantity and membrane localization ofE-cadherin in different cell types.
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