SEQUENTIAL DECREASE IN TIGHT JUNCTIONS AS REVEALED BY 7H6 TIGHT JUNCTION-ASSOCIATED PROTEIN DURING RAT HEPATOCARCINOGENESIS

A sequential decrease in the number of hepatocyte tight junctions duri ng the course of rat hepatocarcinogenesis was demonstrated by immunohi stochemistry with a new 7H6 monoclonal antibody generated in our labor atory. Semiquantitative analysis by confocal laser scanning microscopy revealed that the expression of 7H6 antigen was reduced in hyperplast ic foci, hyperplastic nodules and hepatocellular carcinomas (HCC) to 4 3%, 28% and 25%, respectively, compared to corresponding normal liver tissues. 7H6 antigen was scarce in HCC with a trabecular pattern, wher eas it was expressed intensely at the apical and basolateral membrane of HCC with a glandular pattern. Immunoblot analysis of 7H6 expression in hepatocellular carcinomas showed a decrease roughly coincident wit h that shown by immunohistochemistry. These results indicated, for the first time, that tight junctions decrease progressively during carcin ogenesis, leading to disruption of cellular polarity and cellular adhe siveness.