Yaginuma Y, Westphal H
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
Cancer Res. 1991 Dec 15;51(24):6506-9.
The inactivation of the tumor suppressor gene p53 has been demonstrated in a variety of human tumors. In this study, we present a p53 gene analysis of 13 uterine carcinoma cell lines. Sequencing analysis of the entire coding region revealed mutations changing the p53 amino acid composition in all six endometrial carcinoma cell lines tested (Ishikawa, Hecl-A, Hecl-B, KLE, RL95-2, and AN-3). Of the seven cervical carcinoma cell lines, two (HT-3 and C-33A) contained p53 codon changes as well. We were unable to detect human papillomavirus in these two cell lines. By contrast, five human papillomavirus-positive cervical carcinoma cell lines (HeLa S-3, Caski, SiHa, C-4I, and ME-180) contained wild-type p53 gene sequences. We suggest that, in the human papillomavirus-positive cervical tumors, p53 inactivation occurred via the known mechanism of viral E6/cellular p53 protein association, whereas in all other tumors p53 function was compromised by changes in the amino acid sequence.
肿瘤抑制基因p53的失活已在多种人类肿瘤中得到证实。在本研究中，我们对13种子宫癌细胞系进行了p53基因分析。对整个编码区的测序分析显示，在所有检测的6种子宫内膜癌细胞系（石川细胞系、Hecl-A、Hecl-B、KLE、RL95-2和AN-3）中均发现了改变p53氨基酸组成的突变。在7种宫颈癌细胞系中，有2种（HT-3和C-33A）也存在p53密码子变化。我们在这两种细胞系中未检测到人乳头瘤病毒。相比之下，5种人乳头瘤病毒阳性的宫颈癌细胞系（HeLa S-3、Caski、SiHa、C-4I和ME-180）含有野生型p53基因序列。我们认为，在人乳头瘤病毒阳性的宫颈肿瘤中，p53失活是通过病毒E6/细胞p53蛋白结合的已知机制发生的，而在所有其他肿瘤中，p53功能因氨基酸序列的改变而受损。
