Trial of Gene Therapy for Hepatocellular Carcinoma

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We investigated formation of gap junction (GJ), which has a function of cell to cell communication and differential expression of alpha-fetoprotein (AFP) and albumin (ALB) in ontogenesis of the liver to clarify a role for differentiation of hepatocytes.Connexin (Cx) 32 which is a subunit protein of GJ was expressed before birth by northern blot, and expression of Cx32 and Cx26 were increased after birth. Immunofluorescent study in gestational period showed large plaques of Cx32, and Cx32-and Cx26-positive plaques were scatteredly seen on some hepatocytes. AFP expression by in situ hybridization and immunocytochemistry was seen in all hepatocytes and ALB was already expressed in some hepatocytes. Just after birth Cx32-and Cx26-positive plaques were increased and GJ was ultrastructurally seen. AFP expression was decreased and ALB was expressed in all hepatocytes. A week after birth Cx32-positive small plaques were diffusely distributed in all hepatocytes and Cx26-positive plaques were localized in periporta tract, and structure of GJ was increased in number. AFP expression was remained in a few hepatocytes of central area and ALB expression was accentuated in portal tract.These findings suggest that formation of GJ in ontogenesis of the liver is closely related with differential expression of AFP and ALB,and compulsory expression of Cx may induce well differentiation in hepatoma cells and lead to one of gene therapy for hepatoma.