亚硝基胍诱发大鼠胃腺癌发生发展过程中p53、ras基因表达和突变的研究  

Expression and mutation of p53 and H ras genes in the carcinogenesis and development of gastric adenocancinoma induced by MNNG in rats

作　　者：孟振行[1,2] 雷道年[1,2] 王江 吴晓[1,2] 李豪侠[1,2] 郭山春 

机构地区：[1]北京医科大学病理学系 [2]河南医科大学病理学教研室

出　　处：《中华病理学杂志》1998年第2期117-119,共3页Chinese Journal of Pathology

摘　　要：目的探讨ｐ５３、ｒａｓ基因在亚硝基胍（ＮｍｅｔｈｙｌＮ′ｎｉｔｒｏＮｎｉｔｒｏｓｏｇｕａｎｉｄｉｎｅ，ＭＮＮＧ）诱发大鼠胃腺癌发生发展过程中的作用。方法用免疫组织化学、聚合酶链反应单链构象多态性分析（ＰＣＲＳＳＣＰ）技术对大鼠正常腺胃粘膜、癌前病变和胃腺癌组织中ｐ５３，ｒａｓ基因的表达和突变进行检测。结果ｐ５３蛋白在癌组织中的阳性表达率为５０％（２０／４０只），正常和癌前病变组织中为阴性；ｒａｓ蛋白（ｐ２１）癌前病变组织中阳性率为４４％（２３／５２只），在癌组织中为２３％（９／４０只）。癌组织中ｐ５３基因突变率为４５％（１８／４０只），非癌组织为阴性。癌组织及癌前病变组织中均未发现ｒａｓ基因突变。结论在ＭＮＮＧ诱发大鼠胃腺癌发生发展过程中，ｒａｓ基因的激活是一早期事件，可能参与了癌的发生过程，而ｐ５３突变则主要与胃癌的进展有关。Objective To investigate the effect of p53 and H ras genes in the carcinogenesis of and development of gastric cancer induced by N methyl N′ nitro N nitrosoguanidine (MNNG) in Wistar rats. Methods The expression of p53 and H ras genes in normal mucosa, precancerous lesions and induced cancers were studied immunohistochemically. DNA isolated from the precancerous lesion and tumors were analysized by PCR SSCP for exon 5 8 of p53 gene and exon 1 and 2 of H ras gene. Results p53 protein were detected in 50% (20/40) of the gastric cancers studied, but not in the precancerous lesion, while p21 ras protein seen in 23% (9/40) of the gastric cancers and 44% (23/52) of the precancerous lesions. p53 gene mutations were detected in 45% (18/40) of the cancers and none in the precancerous lesions by PCR SSCP. H ras gene mutation was not found in either the cancers or the precancerous lesions. Conclusions The activation of ras gene is an early event and may be involved in the carcinogenesis of gastric cancer induced by MNNG. Inactivaton of p53 gene may influence the development of the cancer.

关 键 词：胃肿瘤 P53 RAS基因 基因突变 

分 类 号：R735.202[医药卫生—肿瘤]