Expression of a hepatocyte membrane antigen during hepatocarcino-genesis of the rat. -analysis by a monoclonal antibody-

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Changes in the expression of a cell membrane antigen during hepatocarcinogenesis were analyzed by HAM.4, a monoclonal antibody against a membrane glycoprotein of mormal rat hepatocyte. Neoplastic hepatic lesions were induced in rats by DEN, 2-AAF and pertial hepatectomy. Localization of HMA.4 antigen during hepatocarcinogenesis was determined immunohistochemically using HMA.4. In the adult rat liver, HAM.4 antigen was predominantly located on the bile canalicular face (BC). Also, it was stained irregularly on dilated BC of neoplastic foci. On the other hand, the expression of HAM.4 antigen began to diminish partially from the cell membrane in the late nodules. Well differentiated trabecular hepatocellular carcinomas retained HAM.4 antigen, but poorly differentiated and solid hapatomas were not stained by HAM.4. The above findings strongly suggest that HAM.4 antigen is associated with differentiation (or maturation) of rat hapatocytes. The molecular size of HAM.4 antigen is approximately 110 KDa by SDS-PAGE. Although the localization of GGT and HAM.4 antigen is similar in the rat liver, the expression of HAM.4 antigen in the developing liver is quite different from that of GGT. HAM.4 may prodive a means to analyze the characteristics of the rat hepatocyte, especially of their bile canalicular face in terms of differentiation and malignent transformation.