C-fos、K-ras蛋白在肝内胆管癌形成过程中的表达及意义

Expression of C-fos and K-ras proteins during carcinogenesis of intrahepatic cholangiocarcinoma and its significance

目的:探讨癌基因产物C-fos、K-ras蛋白与肝内胆管癌发生的关系及其生物学意义。方法:利用氨基比林和亚硝酸钠诱发叙利亚地鼠肝内胆管癌,应用免疫组化方法检测癌变过程中C-fos、K-ras蛋白的表达情况,并应用图象分析技术对免疫组化结果进行半定量分析。结果:C-fos蛋白在胆管增生病变中即出现高表达,随增生程度的加重及肿瘤形成,其阳性表达率和表达强度均逐渐增高,这种高表达状态持续出现于癌变的全过程;而K-ras蛋白高表达仅见于少数不典型增生胆管、胆管腺瘤和腺癌组织中。结论:c-fos癌基因的激活和蛋白高表达是叙利亚地鼠肝内胆管癌发生的早期分子事件,并参与癌变的全过程;k-ras基因的激活及蛋白高表达可能与部分胆管上皮的恶性转化相关。

Objective:To approach the relationship between oncogene C-fos,K-ras and intrahep atic cholangiocarcinoma (ICC)and the significance.Method:ICC was success ful ly in duced in syrian ham sters by aminopyrine and ni trite.The ex pression of C-fos,K-ras was detected by im munohis to chem istry dur ing ICC carcinogenesis and was semiquanti tative analyzed through analysis of im age pattern.Re sult:An over-expression of C-fos protein was found in intra hepatic bile duct hyperpla sia,and the expred dion level and the positive rates of expression rose grad ually along with the development of hyperpla sia and in the course of ICC carcinogen esis.However,overex pression of K-ras pro tein was found on ly in a few cases of atypi cal hyperpla sia,adenoma and ICC.Conclu sion:The acti vation of c-fos genes and the overex pression of C-fos pro tein may be not only early events but also pre sent in the en tire course of ICC carcinogenesis.The ac-tivation and overexpression of K-ras pro tein may only be related to some cases of ma lig nant transform ing of epitheial cells in the bile duct.