口腔扁平上皮癌におけるHeadpin遺伝子(セリン・プロテアーゼ・インヒビター: serpinファミリー)の発現減弱と過メチル化

摘要

Headpin, which is located at chromosome 18q21.3, belongs to serine proteinase inhibitor family (serpin). One of the functions of this gene family is believed to inhibit hemangiogenesis, invasion, and metastasis of tumors. In this study, 30 clinical tissue specimens of oral squamous cell carcinoma (OSCC) and 9 OSCC-derived cell lines were examined for the down regulation of the gene expression. In addition, the restoration of headpin mRNA expression induced by 5-Aza-2u27-deoxycytidine (5-AzaC) treatment, a DNA demethylating agent, was evaluated in OSCC-derived cell lines. RT-PCR revealed the down-regulation of headpin gene expression in 17 (56.7%) of 30 primary OSCC samples and in 5 (55.6%); SAS, HSC-3, OK92, HO-1-N-1 and SCC4, of 9 OSCC-derived cell lines. Among those 5 cell lines, 5-AzaC treatment induced the restoration of headpin gene expression in 4 (80.0%) cell lines; SAS, HSC-3, OK92 and SCC4. These results suggested that the down-regulation of headpin expression contributes to the development of human OSCC and that DNA hypermethylation is one of the important mechanisms inactivating the headpin gene in oral carcinogenesis.