Mutation and aberrant expression of Caveolin-1 in human oral squamous cell carcinomas and oral cancer cell lines.
Mutation and aberrant expression of Caveolin-1 in human oral squamous cell carcinomas and oral cancer cell lines.
复制标题
DOI：
10.3892/ijo.24.2.435
复制
发表时间：
2004-02
影响因子：
5.2
通讯作者：
Song Ee Han;Kyung-Hee Park;Gene Lee;Yoonee Huh;B. Min
中科院分区：
文献类型：
--
作者：
Song Ee Han;Kyung-Hee Park;Gene Lee;Yoonee Huh;B. Min
Caveolin-1是一种肿瘤抑制基因，在几种类型的人类癌症中被发现因结构异常或表观遗传变化而失活。为探讨小窝蛋白-1在口腔鳞状细胞癌发病机制中的作用，对74例口腔鳞状细胞癌和15个口腔癌细胞系进行了小窝蛋白-1基因外显子1和外显子3的序列分析。此外，还检测了15个口腔癌细胞系中Caveolin-1的表达。在5例癌组织中发现了Cavelin-1基因突变，其中1例为错义突变，4例为沉默突变，突变均位于外显子3。在含有Cavelin-1基因突变的癌组织中，53例在第141密码子上存在从Ile(ATT)到Phe(TTT)的错义突变，在第112、163密码子上存在2个沉默突变。例27、44和84在密码子82由GAC(Asp)突变为GAT(Asp)，在密码子132由CCA(Pro)突变为CCT(Pro)。病例89在密码子84、124和161处有三个沉默突变。然而，在正常口腔角质形成细胞、人乳头瘤病毒永生化的口腔角质形成细胞和15种口腔癌细胞系中没有观察到小窝蛋白-1基因的突变。尽管有完整的小窝蛋白-1基因，但口腔癌细胞株Hep-2缺乏小窝蛋白-1蛋白。相比之下，两种癌细胞株KOSCC-25C和-33B的小凹蛋白-1含量微乎其微。这些结果提供了遗传学证据，表明Caveolin-1通过突变或表达减少而失活，可能在口腔癌的发病机制中发挥作用。
Caveolin-1, a tumor suppressor gene, was found to be inactivated by structural abnormalities or epigenetic changes in several types of human cancers. In order to investigate the role of Caveolin-1 in the pathogenesis of human oral squamous cell carcinoma, the exon 1 and 3 sequences of the Caveolin-1 were investigated in 74 oral squamous cell carcinomas and 15 oral cancer cell lines. In addition, Caveolin-1 expression was examined in 15 oral cancer cell lines. Mutations of the Caveolin-1 gene were identified in five cancers (1 missense and 4 silent mutations), with all mutations being detected in exon 3. Among the cancers containing the Caveolin-1 mutation, case 53 harbored a missense mutation from Ile (ATT) to Phe (TTT) at codon 141 and two silent mutations at codons 112 and 163 of the Caveolin-1 gene. Cases 27, 44, and 84 had two silent mutations from GAC (Asp) to GAT (Asp) at codon 82, and from CCA (Pro) to CCT (Pro) at codon 132. Case 89 contained three silent mutations at codons 84, 124, and 161. However, mutations of the Caveolin-1 gene were not observed in normal human oral keratinocytes, the human papillomavirus-immortalized oral keratinocytes, and 15 oral cancer cell lines. Despite the intact Caveolin-1 gene, one oral cancer cell line, HEp-2, lacked the caveolin-1 protein. In contrast, two cancer cell lines, KOSCC-25C and -33B, had an insignificant amount of the caveolin-1 protein. These results provide genetic evidence showing that the inactivation of Caveolin-1 by a mutation or by reduced expression may play a role in the pathogenesis of oral cancer.