p53 mutations in hepatocellular carcinomas induced by a choline-devoid diet in male Fischer 344 rats.
p53 mutations in hepatocellular carcinomas induced by a choline-devoid diet in male Fischer 344 rats.
复制标题
雄性 Fischer 344 大鼠缺乏胆碱饮食诱导的肝细胞癌中的 p53 突变。
DOI：
10.1093/carcin/14.3.503
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发表时间：
1993
期刊：
影响因子：
4.7
通讯作者：
Lombardi,B
中科院分区：
文献类型：
--
作者：
Smith,ML;Yeleswarapu,L;Scalamogna,P;Locker,J;Lombardi,B
对喂食无胆碱饮食的雄性Fischer 344大鼠的肝脏和肝细胞癌进行分析，以评估它们是否携带p53肿瘤抑制基因的改变。分析包括用抗p53单克隆抗体对组织切片进行免疫过氧化物酶染色、Western印迹和cDNA测序。免疫染色显示，在22/27分析的肿瘤和免疫印迹在18/20的突变p53蛋白的存在。获得的免疫化学证据表明，突变的发生先于肿瘤的发展。对11例表达突变型p53基因蛋白的肝细胞癌进行cDNA测序。发现7个在基因的120-290密码子区域内含有点突变，1个在同一区域内存在微缺失。未观察到突变热点。可以得出结论，p53基因内的突变，沿着与c-mycgene扩增先前在这些肿瘤中检测到的，最有可能有助于肝细胞的肿瘤转化，在这种营养模型的肝癌。结果也进行了讨论，鉴于最近的文献中存在的p53突变在人肝细胞癌。
Analyses were performed on livers and hepatocellular carcinomas from male Fischer 344 rats fed a choline-devoid diet, to assess whether they carried alterations of the p53 tumor suppressor gene. The analyses consisted of immunoperoxidase staining of tissue sections with monoclonal antibodies to p53, Western blotting and cDNA sequencing. Immunostaining revealed the presence of mutant p53 proteins in 22/27 tumors analyzed and immunoblotting in 18/20. Immunochemical evidence was obtained that occurrence of the mutations precedes tumor development. cDNA sequencing was performed on 11 hepatocellular carcinomas that expressed mutant p53 gene proteins. Seven were found to contain point mutations within the 120–290 codon region of the gene, and one a microdeletion in the same region. No mutational hot spot was observed. It is concluded that mutations within the p53 gene, along with a c-mycgene amplification previously detected in these tumors, most likely contribute to the neoplastic transformation of liver cells in this nutritional model of hepatocarcinogenesis. The results are discussed also in view of recent literature on the presence of p53 mutations in human hepatocellular carcinomas.