p53 gene mutations and p21 protein expression induced independently of p53, by TGF-β and γ-rays in squamous cell carcinoma cells

p53 gene mutations and p21 protein expression induced independently of p53, by TGF-β and γ-rays in squamous cell carcinoma cells
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DOI:
10.1016/s0959-8049(98)00291-3
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发表时间:
1999-02-01
影响因子:
8.4
通讯作者:
Osaki, T
Osaki, T
中科院分区:
医学1区
文献类型:
--
作者:
Yoneda, K;Yokoyama, T;Osaki, T

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本文研究了9株颈淋巴结转移性鳞癌细胞系(OSC-1 ~ OSC-9)p53基因突变及TGF-β和γ射线对p21启动子活性、p21 mRNA和蛋白表达的影响。p53基因外显子2至11的直接DNA序列分析显示,在所有细胞系中有16个点突变,但没有观察到缺失或添加。TGF-β上调p21启动子活性约为对照的2倍,同时增加p21 mRNA表达,但OSC-8和-9除外。然而,尽管除OSC-8和OSC-9外,照射细胞中的p21 mRNA表达增加,但γ射线抑制了p21启动子活性。与信使表达平行,TGF-β强烈增加p21蛋白表达,但γ射线仅微弱增加。这些结果表明,p53基因的点突变是常见的转移性SCC细胞和p21 mRNA的表达是p53独立诱导的TGF-β和γ射线,虽然TGF-β和γ射线的诱导机制是不同的。(C)1999爱思唯尔科技有限公司。保留所有权利。
p53 gene mutation and the influence of TGF-beta and gamma-rays on p21 promoter activity, p21 mRNA and protein expression were investigated in nine cell lines (OSC-1 to -9) established from metastatic squamous cell carcinomas (SCC) of the cervical lymph nodes. The direct DNA sequence analysis of exons 2 to 11 of the p53 gene revealed 16 point mutations in all cell lines, but neither deletions nor additions were observed. TGF-beta upregulated p21 promoter activity by approximately 2-fold of the control and concurrently increased p21 mRNA expression, except in OSC-8 and -9. However, gamma-rays suppressed p21 promoter activity, although p21 mRNA expression in irradiated cells was increased except for OSC-8 and -9. In parallel with the messenger expression, p21 protein expression was strongly increased by TGF-beta, but only weakly increased by gamma-rays. These results indicate that point mutation of the p53 gene is frequent in metastatic SCC cells and p21 mRNA and its protein expression is p53-independently induced by both TGF-beta and gamma-rays, although the mechanism of induction by TGF-beta and gamma-rays is different. (C) 1999 Elsevier Science Ltd. All rights reserved.