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

应用抗正常大鼠肝细胞膜糖蛋白的单克隆抗体HAM.4，分析了肝癌发生过程中细胞膜抗原表达的变化。用DEN、2-AAF和部分肝切除术诱发大鼠肝癌。肝癌发生过程中HMA.4抗原的定位用HMA.4免疫化学法测定。在成年大鼠肝脏中，HAM.4抗原主要位于胆小管表面（BC）。在肿瘤病灶的扩张CT上也呈不规则染色。另一方面，HAM.4抗原的表达在晚期结节中开始从细胞膜部分减少。高分化小梁型肝细胞癌保留HAM.4抗原，而低分化和实性肝癌不被HAM.4染色。上述发现有力地表明，HAM.4抗原与大鼠肝细胞的分化（或成熟）有关。经SDS-PAGE分析，HAM.4抗原的分子大小约为110 KDa。虽然GGT和HAM.4抗原在大鼠肝脏中的定位相似，但HAM.4抗原在发育中的肝脏中的表达与GGT的表达完全不同。HAM.4为分析大鼠肝细胞的特性，特别是胆管面的分化和转化提供了一种手段。

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.