Expression of wild-type p53 in human A673 cells suppresses tumorigenicity but not growth rate.
Expression of wild-type p53 in human A673 cells suppresses tumorigenicity but not growth rate.
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发表时间：
1991-10
期刊：
影响因子：
8
通讯作者：
Chen Ym;Chen Pl;N. Arnaiz;D. Goodrich;Lee Wh
中科院分区：
文献类型：
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作者：
Chen Ym;Chen Pl;N. Arnaiz;D. Goodrich;Lee Wh
已经发现p53基因在许多不同种类的人类癌症中发生突变。在以前的研究中，通过逆转录病毒介导的基因转移在人骨肉瘤细胞中表达外源性野生型p53导致细胞大小显著增大，培养中生长速率降低，并且在裸鼠中致瘤性丧失。在这里，我们研究野生型或突变的p53对人外周神经上皮瘤（PNET）A673细胞表达的影响，这些细胞含有明显正常的等位基因的p53基因，但不表达可检测量的p53蛋白。p53表达细胞的各种特性进行了检查，包括形态，生长速度，软琼脂集落形成，和裸鼠的致瘤性。与骨肉瘤Saos-2细胞相比，野生型或突变型p53蛋白在A673细胞中的表达对形态学或生长特性没有影响。然而，表达野生型p53蛋白的克隆在软琼脂中形成集落和在裸鼠中形成肿瘤的能力降低。为了证实野生型p53表达细胞的基因型，通过聚合酶链反应扩增一个细胞克隆的前病毒p53编码DNA并测序。我们得出结论，野生型p53基因的单个等位基因的表达足以抑制PNET A673致瘤性，但对培养物中的生长速率没有可检测的影响。
The p53 gene has been found to be mutated in many different kinds of human cancers. In a previous study, expression of exogenous wild-type p53 in human osteosarcoma cells by retrovirus-mediated gene transfer resulted in marked enlargement of cell size, reduced growth rate in culture and loss of tumorigenicity in nude mice. Here we examine the effects of expression of wild-type or mutated p53 on human peripheral neuroepithelioma (PNET) A673 cells; these cells contained apparently normal alleles of the p53 gene but did not express a detectable quantity of p53 protein. Various characteristics of the p53-expressing cells were examined including morphology, growth rate, soft-agar colony formation, and tumorigenicity in nude mice. In contrast to osteosarcoma Saos-2 cells, expression of wild-type or mutant p53 protein in A673 cells had no effect on morphology or growth characteristics. However, clones expressing wild-type p53 protein had reduced ability to form colonies in soft agar and tumors in nude mice. To substantiate the genotype of wild-type p53-expressing cells, the proviral p53-encoding DNA of one cell clone was amplified by the polymerase chain reaction and sequenced. We concluded that expression of a single allele of the wild-type p53 gene was sufficient to suppress PNET A673 tumorigenicity but had no detectable effect on growth rate in culture.