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.