TUMOR PROMOTERS INDUCE INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION IN MOUSE EPIDERMAL-CELLS BY AFFECTING THE LOCALIZATION OF CONNEXIN43 AND E-CADHERIN
L. Jansen et al., TUMOR PROMOTERS INDUCE INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION IN MOUSE EPIDERMAL-CELLS BY AFFECTING THE LOCALIZATION OF CONNEXIN43 AND E-CADHERIN, Environmental toxicology and pharmacology, 1(3), 1996, pp. 185-192
The molecular and histological effects of tumor promoters on gap junct
ional intercellular communication (GJIC) were studied in three mouse e
pidermal cell types, representing different stages of tumor formation.
GJIC was inhibited by most of the studied compounds (L-ethionine, d-l
imonene, o-anisidine, clofibrate, Aroclor 1260 and 1,1'-(2,2,2-trichlo
roethylidene)bis(4-chlobenzene) (DDT)) except NaF and phenobarbital (P
B). Whatever their effect on GJIC, most of the studied compounds incre
ased the phosphorylation state of the gap junction protein expressed i
n these cells, connexin43 (Cx43), as shown by Western analysis. All ag
ents with GJIC inhibiting capacity changed the intensity of the immuno
fluorescent 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 membran
e and/or cytosolic staining) and Cx43 phosphorylation or GJIC inhibiti
on. 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. Howe
ver, all agents which decreased GJIC, affected E-cadherin immunostaini
ng of the membrane, while PB and NaF had no effect. These results show
that an association exists between inhibition of GJIC and localizatio
n of both connexin43 and E-cadherin protein, but not with Cx43 phospho
rylation.