title: Tumor promoters induce inhibition of gap junctional intercellular communication in mouse epidermal cells by affecting the localization of connexin43 and E-cadherin.
abstract: The molecular and histological effects of tumor promoters on gap junctional intercellular communication (GJIC) were studied in three mouse epidermal cell types, representing different stages of tumor formation. GJIC was inhibited by most of the studied compounds (l-ethionine, d-limonene, o-anisidine, clofibrate, Aroclor 1260 and 1,1'-(2,2,2-trichloroethylidene)bis(4-chlorobenzene) (DDT)) except NaF and phenobarbital (PB). Whatever their effect on GJIC, most of the studied compounds increased the phosphorylation state of the gap junction protein expressed in these cells, connexin43 (Cx43), as shown by Western analysis. All agents with GJIC inhibiting capacity changed the intensity of the immunofluorescent staining of Cx43 on the membrane of the cells, whereas NaF and PB had no effect on Cx43 immunostaining. No association could be found between the type of change in Cx43 localization (changed membrane and/or cytosolic staining) and Cx43 phosphorylation or GJIC inhibition. Because the cell adhesion molecule E-cadherin also regulates GJIC, the effects of tumor promoters on E-cadherin protein and localization were studied. No quantitative change could be observed in E-cadherin protein content of cells treated with any of the selected agents. However, all agents which decreased GJIC, affected E-cadherin immunostaining of the membrane, while PB and NaF had no effect. These results show that an association exists between inhibition of GJIC and localization of both connexin43 and E-cadherin protein, but not with Cx43 phosphorylation.
authors.affiliation: Agrotechnological Research Institute (ATO-DLO), Department of Product Quality and Safety, P.O. Box 17, 6700 AA Wageningen, Netherlands; Agricultural University Wageningen. Department of Toxicology, Tuinlaan 5, 6703 HE Wageningen, Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Jansen
authors.forename: M
authors.initials: M
authors.lastname: Mesnil
authors.forename: J
authors.initials: J
authors.lastname: Koeman
authors.forename: W
authors.initials: W
authors.lastname: Jongen