实验性大鼠肝癌形成过程中c-myc、Ha-ras、Ki-ras的表达特点及其生物意义  

Study on expressive characteristic and biological significance of cmyc、Haras and Kiras during experimental rat hepatocarcinogenesis

作　　者：薛玲[1] 赵国强[1] 胡瑞德[1] 董郡[1] 

机构地区：[1]广州中山医科大学病理教研室

出　　处：《癌症》1998年第1期4-6,F004,共4页Chinese Journal of Cancer

基　　金：卫生部回国人员启动基金

摘　　要：目的：通过动态观察ｃ－ｍｙｃ、Ｈａ－ｒａｓ和Ｋｉ－ｒａｓ在实验性大鼠肝癌形成过程中的表达变化，探讨上述原癌基因与肝癌发生的关系及其生物学意义。方法：用３＇－Ｍｅ－ＤＡＢ饲喂ＳＤ大鼠，分别于第４，６，８，１４和１７周处死大鼠，取其肝脏，石蜡包埋，并进行核酸原位杂交。结果：在诱癌全过程中，ｃ－ｍｙｃ和Ｈａ－ｒａｓ均为同步表达；在诱癌的早期即可检测到较多ｃ－ｍｙｃ和Ｈａ－ｒａｓ的阳性表达细胞，而Ｋｉ－ｒａｓ的细胞数则很少，且反应强度弱；而诱癌后期，各癌基因ｍＲＮＡ阳性表达细胞均减少；至第１７周，所有癌组织内均显示三种癌基因表达阴性，或仅见个别小癌巢内少数癌细胞呈弱阳性。而癌旁肝组织内却可见三种癌基因的大量表达。结论：ｃ－ｍｙｃ和Ｈａ－ｒａｓ被激活是肝癌发生过程中的早期事件，且二者之间具有协同作用，这种协同作用在肝癌的启动上可能具有重要意义；Ｋｉ－ｒａｓ的激活则发生较晚，可能与促进细胞恶性转化有关。Purpose: To explore the relationship between oncogenes and carcinogenesis of liver as well as the significance by dynamically observation of the expression change of cmyc、Haras and Kiras during the experimental hepatocarcinogenesis of rats. Methods: SD rats were fed by 3′MeDAB and killed in 4、6、8、14、and 17th week respectively.The livers of rars were isolated and embedded by paraffin and the in situ hybridization was made .Results:The expression and distribution of Haras and cmyc were the same in the liver sections from different periods of cancer induction.In early stage of carcinoma induction,we can detect more positive cells of Haras and cmyc but little Kiras positive cells.In late stage of carcinoma induction,the positive cells of three oncogenes decreased and in 17th week all of carcinoma nodules were negative or weak positive for three oncogenes but were strong positive in liver tissue around carcinoma.Conclusion: There was a special cooperation in Haras and cmyc that is very important for the malignant transformation of cells in the early stage of hepatocarcinogenesis,but two oncogens might play no role in the late stage of this process,in which carcinoma had been formed.Kiras was detected only in the tissue around carcinoma. It indicated Ki-ras might be activated in the late stage of carcinoma induction and related to the promotion of cell malignant transformation.

关 键 词：肝肿瘤 原位杂交 C-MYC基因 Ha-ras基因 

分 类 号：R735.702[医药卫生—肿瘤]