Ineffectiveness of the presence of H-ras/p53 combination of mutations in squamous cell carcinoma cells to induce a conversion of a nontumorigenic to a tumorigenic phenotype
Ineffectiveness of the presence of H-ras/p53 combination of mutations in squamous cell carcinoma cells to induce a conversion of a nontumorigenic to a tumorigenic phenotype
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DOI：
10.1023/a:1007419810705
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发表时间：
1997-10-01
影响因子：
6.1
通讯作者：
Milo, GE
中科院分区：
文献类型：
--
作者：
Lee, H;Li, D;Milo, GE
人肿瘤细胞在体外或在替代宿主中具有不同于正常细胞的特性，如永生性、锚定独立性和裸鼠中的肿瘤形成。然而，来自个体肿瘤的不同细胞可能表现出一些，但不是所有这些特征。在过去的几年中，已经研究了来自不同肿瘤和组织类型的人肿瘤细胞系，以确定与上述体外特性和裸鼠致瘤性相关的分子变化。在本研究中，7个细胞系来源于人类肿瘤的特点是p53和ras突变，可能发生在SCC肿瘤表型和裸鼠的肿瘤形成。本研究旨在检查突变ras和p53的共同出现是否导致进展过程中的恶性阶段。7个细胞系中没有一个在p53肿瘤抑制基因的公认的“热点”中含有突变，但是4个在密码子126中有无义/剪接突变，在H-ras基因的密码子12中有突变。其余三个细胞系分别在内含子5、密码子193和密码子126中具有p53突变。7个细胞系中有4个是非致瘤性的;其中2个细胞系含有无义p53-126突变和突变的ras; 1个细胞系在密码子126处有错义突变，但没有突变的ras;第4个细胞系在密码子193处只有p53突变。在用甲磺酸甲酯或N-甲基-N '-硝基-N-亚硝基胍处理后，两种非致瘤细胞系转化为致瘤细胞，两种基因均无明显的额外突变。我们的分析表明，有一个高频率的遗传多样性和突变的p53和H-ras。p53突变的存在与细胞在裸小鼠中表现出恶性潜力的能力之间也缺乏因果关系。
Human tumor cells have properties in vitro or in surrogate hosts that are distinct from those of normal cells, such as immortality, anchorage independence, and tumor formation in nude mice. However, different cells from individual tumors may exhibit some, but not all of these features. In previous years, human tumor cell lines derived from different tumor and tissue types have been studied to determine those molecular changes that are associated with the in vitro properties listed above and with tumorigenicity in nude mice. In the present study, seven cell lines derived from human tumors were characterized for p53 and ras mutations that may occur in SCC tumor phenotypes and for tumor formation in nude mice. This investigation was designed to examine whether co-occurrence of mutated ras and p53 lead to a malignant stage in the progression process. None of the seven cell lines contained mutations in the recognized ''hot spots'' of the p53 tumor suppressor gene, but four had a nonsense/splice mutation in codon 126 and a mutation in codon 12 of the H-ras gene. The remaining three cell lines had p53 mutations in intron 5, in codon 193, and a missense mutation in codon 126, respectively. Four of seven cell lines were nontumorigenic; two of these cell lines contained a nonsense p53-126 mutation and mutated ras; one had a missense mutation at codon 126 but no mutated ras; the the fourth had only a p53 mutation at codon 193. Two of the nontumorigenic cell lines were converted to tumorigenicity after treatment with methyl methanesulfonate or N-methyl-N'-nitro-N-nitrosoguanidine with no apparent additional mutations in either gene. Our analysis revealed that there was a high frequency of genetic diversity and mutations in both p53 and H-ras. There was also a lack of a causal relationship in the presence of mutations in p53 and the cells' ability to exhibit a malignant potential in nude mice.