Reduced expression and hypermethylation of HEADPIN, a serine proteinase inhibitor (serpin) in human squamous cell carcinoma

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 13672122
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Tokyo Dental College
• Principal Investigator: TAKEDA Eizo TOKYO DENTAL COLLEGE, DEPARTMENT OF DENTISTRY, ASSISTANT, 歯学部, 助手 (20322472)
• Co-Investigator(Kenkyū-buntansha): KATAKURA Akira TOKYO DENTAL COLLEGE, DEPARTMENT OF DENTISTRY, LECTURER, 歯学部, 講師 (10233743) ; UZAWA Katuhiro CHIBA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSISYANT PROFESSOR, 医学部, 助教授 (30302558) ; SHIBAHARA Takahiko TOKYO DENTAL COLLEGE, DEPARTMENT OF DENTISTRY, ASSISTANT PROFESSOR, 歯学部, 助教授 (50178919)
• Project Period (FY): 2001 – 2003
• Keywords: HEADPIN gene / oral squamous cell carcinoma / 口腔癌

Research Abstract

Our in-house cDNA microarray system, which carries cDNAs derived from oligo-capped eDNA library of human oral cavity cancer cell lines, identified reduced expression of several genes in oral squamous cell carcinoma (OSCC). Thirteen genes were down-regulated 0.5-fold or more in common among four OSCC specimens of independent cases, compared with normal tissues. Among these genes, HEADPIN, which was isolated at chromosome 18q21.3, belongs to the member of serine proteinase inhibitor family (serpin). One of the functions of this gene family is believed to inhibit heamangiogenesis, invasion, and metastasis of tumors. RT-PCR revealed the down-regulation of HEADPIN gene expression in 17 (56.7%) of 30 primary OSCC samples and in 6 (66.7%) of 9 cell lines derived from OSCC. Furthermore, restoration of the HEADPIN gene mRNA was induced in five of six OSCC-derived cell lines showing down-regulation of the gene expression after treatment with 5-aza-2'-deoxycytidine, a DNA demethylating agent. Thus, the down-regulation of HEADPIN expression contributes to the development of human OSCC and hypermethylation of the gene was confirmed to be one of the important mechanisms of inactivation of the HEADPIN gene in oral carcinogenesis.