实验性肝癌糖原和癌基因N-ras表达的研究

THE STUDY OF N ras AND GLYCOGEN EXPRESSION DURING EXPERIMENTAL HEPATOCARCINOGENESIS

通过应用原位杂交和组织化学技术，对二乙基亚硝胺诱发的大鼠肝细胞肝癌中糖原和癌基因Ｎ－ｒａｓ表达的研究，发现从诱癌早期到晚期，肝细胞内的糖原由储积而逐渐丧失。Ｎ－ｒａｓ在诱癌的第１～２周即出现阳性表达，随诱癌过程的延长，阳性表达的细胞数和范围逐渐增加，至诱癌晚期甚至在癌结节内均转为阴性。对肝组织连续切片中糖原和Ｎ－ｒａｓ表达的对比观察发现，糖原ＰＡＳ反应与Ｎ－ｒａｓ反应同步，糖原ＰＡＳ反应具有与Ｎ－ｒａｓ一致的异质性，其阳性与阴性病变分布与Ｎ－ｒａｓ表达重叠。提示Ｎ－ｒａｓ基因表达可能在肝癌的启动过程中发挥重要作用，并且可能涉及对糖原基因的调控。

In order to investigate the relation of oncogenes and glycogen, the expression of N ras and glycogen was studied during early and late stages of DENA induced hepatocarcinogenesis in rats by using in situ hybridization and histochemical method. The results showed that in the early stage, glycogen storage accompanied with expression of N ras was found in many cells. In was interesting that there was also identical heperogeneity in the histochemical reaction for glycogen and the expression of N ras at the late stage of hepatocarcinogenesis, that is ,the glycogen was stored in N ras positive cells, in turn, the glycogen was often lost in N ras negative cells. The results dcmonstratc that the disappearance of N ras expression in late lesions seems to be an index for judging malignancy or precancerous lesion. Abnormal histochemic reaction for glycogen is a relatively specific index to determine malignant change of hepatocytes. The results indicate that the expression of N ras plays an important role in the iuitial process of hepatocarcinoma and is probably in volued in the regulation of glycogen.