INACTIVATION OF THE P53 GENE BY EITHER MUTATION OR HPV INFECTION IS EXTREMELY FREQUENT IN HUMAN ORAL SQUAMOUS-CELL CARCINOMA CELL-LINES
INACTIVATION OF THE P53 GENE BY EITHER MUTATION OR HPV INFECTION IS EXTREMELY FREQUENT IN HUMAN ORAL SQUAMOUS-CELL CARCINOMA CELL-LINES
复制标题
DOI：
10.1016/0964-1955(94)90036-1
复制
发表时间：
1994-09-01
期刊：
影响因子：
--
通讯作者：
PARK, NH
中科院分区：
文献类型：
--
作者：
MIN, BM;BAEK, JH;PARK, NH
在九种人类口腔癌细胞系中研究了 p53 肿瘤抑制因子的状态和高危人乳头瘤病毒 (HPV) 感染的频率。三种癌细胞系（SCC-4、Tu-177 和 FaDu）的 p53 转录物数量与正常细胞相似，但 p53 蛋白水平明显高于正常对照细胞。对这些癌细胞的p53基因高度保守的开放阅读框进行测序显示，SCC-4和Tu-177细胞系中存在点突变，从CCC到TCC的碱基转变发生在密码子151处；在 FaDu 系中，密码子 248 处发生了 CGG 到 CTG 的突变。与正常对应物相比，HEp-2 和 1483 癌细胞系含有显着较低水平的 p53 蛋白。 HEp-2 和 1483 细胞系的 p53 cDNA 测序显示没有突变，但 Northern 分析显示这些细胞系表达 HPV-18 E6/E7 信息。与正常对应物相比，四种细胞系（SCC-9、SCC-15、SCC-25 和 Tu-139）表达的 p53 转录物数量可忽略不计，且 p53 蛋白水平不可检测。这些细胞系在 p53 基因的高度保守的开放阅读框中含有突变，如下所示：SCC-9 在密码子 274 和 285 之间删除了 32 个碱基对； SCC-15 系在密码子 224 和 225 之间插入了 5 个碱基对； SCC-25品系在密码子209中删除了两个碱基对； Tu-139 系在密码子 171 和 186 之间删除了 46 个碱基对。这些数据表明 p53 的异常表达和 p53 蛋白水平的改变在口腔癌细胞系中极为常见，并且这些变化可能是由于突变或高危 HPV 感染造成的。
The state of p53 tumour suppressor and the frequency of high-risk human papillomavirus (HPV) infections were studied in nine human oral cancer cell lines. Three cancer cell lines (SCC-4, Tu-177 and FaDu) had similar amounts of p53 transcripts to normal cells, but contained significantly higher levels of p53 protein than the normal control cells. Sequencing highly conserved open reading frames of the p53 gene of these cancer cells showed point mutations in the SCC-4 and Tu-177 cell lines, a base transition from CCC to TCC occurred at codon 151; and in the Line FaDu, a mutation of CGG to CTG occurred at codon 248. The HEp-2 and 1483 cancer lines contained significantly lower levels of p53 protein compared to the normal counterpart. Sequencing of p53 cDNA for HEp-2 and 1483 lines showed no mutations, but northern analysis revealed that these cell lines expressed HPV-18 E6/E7 messages. Four cell lines (SCC-9, SCC-15, SCC-25, and Tu-139) expressed negligible amounts of p53 transcripts compared to the normal counterpart and undetectable levels of p53 protein. These cell lines contained mutations in the highly conserved open reading frames of the p53 gene as follows: the SCC-9 had a deletion of 32 base pairs between codons 274 and 285; the line SCC-15 had an insertion of five base pairs between codons 224 and 225; the line SCC-25 had a deletion of two base pairs in codon 209; and the Tu-139 line had a deletion of 46 base pairs between codons 171 and 186. These data indicate that aberrant expression of p53 and altered levels of p53 protein are extremely frequent in oral cancer cell lines, and that these changes may result from either mutations or infection with high-risk HPV.