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肝细胞癌mdm2基因表达及其与p53基因突变的关系 被引量:8

mdm2 gene expression in hepatocellular carcinoma and its relationship to p53 gene mutation
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摘要 目的研究mdm2基因在原发性肝细胞癌(HCC)中的表达并探讨其与p53基因突变的关系.方法用银染PCRSSCP法检测p53基因第5~8外显子的突变,原位杂交检测mdm2基因mRNA的表达,SABC法检测mdm2蛋白的表达.结果393%(11/28)的病例有异常的电泳迁移率.p53基因突变与肿瘤的大小、分化及转移无关.原位杂交显示9例HCC出现mdm2基因mRNA增加,7例HCC可检测到mdm2蛋白表达,mdm2基因表达与HCC的大小、分化及是否转移无关.Ⅰ~Ⅱ级HCC中mdm2阳性表达率(133%)明显低于Ⅲ~Ⅳ级HCC中的阳性表达率(538%).11例有p53基因突变的HCC中,只有3例出现mdm2基因表达,另外6例有mdm2过表达的HCC未见p53基因突变.p53基因突变的HCC与p53基因无突变的HCC相比,mdm2基因表达阳性率无显著差别.结论p53基因突变和mdm2基因表达在原发性HCC的发病中起重要作用.mdm2基因表达与HCC的恶性程度相关.mdm2基因表达与p53基因是否突变无关. AIM To estimate the role of mdm2 gene overexpression in primary hepatocellular carcinoma (HCC) and its relationship to p53 gene mutation. METHODS Silver staining PCR SSCP was used to determine exon 5-8 mutation of p53 gene. In situ hybridization (ISH) was employed to detect the mdm2 gene overexpression at mRNA level. Strept avidin biotin enzyme complex method was used for immunohistochemical detection. RESULTS Of the 28 HCC cases examined, 11 (39 3%) showed abnormal band mobility shifts, suggesting the presence of mutations in these exons. No abnormal band shift was found in the noncancerous adjacent liver tissues. p53 gene mutation had no significant correlation to the size, differentiation or metastasis of HCC. Nine out of 28 (32 1%) cases were positive for mdm2 gene transcripts by ISH. About 7 of 28 (25%) cases showed visibly detectable signal for mdm2 protein. Two cases with ISH positive failed to show mdm2 immunoreactivities. The overexpression of mdm2 gene had no correlation with the size, differentiation or metastasis of HCC, but in 15 grade Ⅰ-Ⅱ HCC, 2 (13 3%) harbored mdm2 gene overexpression. It is much lower than that in grade Ⅲ-Ⅳ ( P <0 05), in which 7/ 13 (53 8%) cases possessed mdm2 gene overexpression. Three out of 11 cases with p53 gene mutation demonstrated overexpression of mdm2 gene whereas the remaining 6 cases which showed mdm2 gene overexpression had no p53 gene mutation. There was no correlation between mdm2 gene overexpression and p53 gene mutation. CONCLUSION p53 gene mutation and mdm2 gene overexpression are involved in pathogenesis of HCC. mdm2 expression is associated with the severity of tumors. Overexpression of mdm2 gene is not correlated with mutation of the p53 gene.
出处 《世界华人消化杂志》 CAS 1999年第4期291-292,共2页 World Chinese Journal of Digestology
关键词 肝肿瘤 MDM2基因 P53基因 基因突变 liver neoplasms carcinoma, hepatocellular mdm2 gene p 53 gene gene expression
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