大鼠肝癌发生过程中癌基因和抑癌基因的表达

Expression of oncogene and suppressor gene during experimental hepatocarcinogenesis in rats

探讨癌基因ras和抑癌基因P5 3蛋白在实验性肝癌发生中的表达与内在联系。方法 应用原位杂交和免疫组织化学 (SABC)法 ,在 38例化学致癌剂二乙基亚硝胺 (DENA)诱发大鼠原发性肝细胞癌及癌前增殖结节中 ,观察P5 3蛋白和ras家族基因 (N ras,H ras,Ki ras)蛋白表达。结果 化学诱癌生成为 6 8.42 % (2 6 / 38) ,癌前增生性病例为 31.5 8% (12 / 38)。在癌与增生性病变中ras基因蛋白高表达分别为 88.46 % (2 3/ 2 6 )和 75 % (9/ 12 ) ,两组无显著差异(P >0 .0 5 ) ,但与癌的恶性分化程度密切相关 (P <0 .0 1)。在增生性病灶中未检出P5 3蛋白的表达 ,在癌中P5 3蛋白表达阳性率为 46 .15 % (12 / 2 6 ) ,但与ras蛋白表达无显著相关性 (P >0 .0 5 )。结论 ras基因是肝癌转化较早的分子改变 ;癌前嗜碱性增生性结节和不典型增生性腺瘤结节具有较高的恶化潜能 ;ras和P5

Objective To study the expression of oncogene protein, P21 and suppressor gene P53 in hepatocarcinogenesis.Methods The expressions of P53 and the oncogenes of ras family (N ras,H ras,Ki ras) in hepatocellular carcinoma (HCC) and the proliferating liver cells in precancerous hyperplastic nodules in the rat during experimental hepatocarcinogenesis induced by diethylnitrosamine(DENA), and studied by immunohistochemistry and in situ hybridization.Results The induced rate of hepatic carcinoma was 68.42%(26/38) and that of precancerous hyperplastic nodules 31.58%(12/38). The positive rates of ras gene in HCC and precancerous hyperplastic nodules were 88.46%(23/26) and 75%(9/12), respectively. The positive expressions were not statisticaly different in the two groups, but were related to the degree of malignant differentiation( P <0.01). No P53 protein was expressed in the precancerous hyperplastic nodules but it was present 46.15%(12/26) of HCC. There was no correlations between the expressions of ras and P53 protein.Conclusion Our data indicate that the expression of ras gene is an early event in the initiation of HCC, also being one of the molecular changes in morphogenesis of HCC. The basophilic preneoplastic foci and adenomatous hyperplasia showed high grade malignant potential. The expression of P53 and ras play different roles in the course of tumorigenesis.