E-CADHERIN BUT NOT N-CADHERIN EXPRESSION IS CORRELATED WITH THE INTRACELLULAR-DISTRIBUTION OF CATENINS IN HUMAN HEPATOCELLULAR CARCINOMAS

Cadherins are Ca2+-dependent cell-cell adhesion molecules, and are inv olved in the formation and maintenance of the histo-architecture. Usin g a combination of biochemical and immunohistochemical methods, we ana lyzed the expression of the cadherin-catenin complex in 34 human hepat ocellular carcinomas. Unexpectedly, we found the expression of N (neur al)-cadherin in normal hepatocytes and all hepatocellular carcinomas e xamined. In 18 cases, the decreased expression of E (epithelial)-cadhe rin was observed. Among them, the decreased expression of alpha-cateni n and gamma-catenin (plakoglobin) was also observed in 9 and 6 cases, respectively. Thus the decreased expression of alpha-catenin and gamma -catenin was apparently preceded by the decreased expression of E-cadh erin. The decreased expression of beta-catenin was not observed in any of the cases analyzed. beta-Catenin was found to accumulate in the cy toplasm of hepatocellular carcinomas with the decreased expression of E-cadherin, despite the presence of N-cadherin at the cell-cell contac ts. These results suggest a pivotal role of E-cadherin in the intracel lular distribution of catenins in hepatocellular carcinomas.