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

人鳞状细胞癌中丝氨酸蛋白酶抑制剂 (serpin) HEADPIN 的表达减少和高甲基化

• 批准号: 13672122
• 负责人: TAKEDA Eizo
• 金额: $ 2.24万
• 依托单位: Tokyo Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672122/
• 关键词: HEADPIN gene; oral squamous cell carcinoma; 口腔癌; headpin-gene

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.

我们的内部cDNA微阵列系统，它携带来自人口腔癌细胞系的oligo-capped eDNA文库的cDNA，确定了口腔鳞状细胞癌（OSCC）中几个基因的表达降低。与正常组织相比，13个基因在4个独立病例的口腔鳞癌标本中普遍下调0.5倍或更多。其中HEADPIN基因属于丝氨酸蛋白酶抑制剂家族（serine proteinase inhibitor family，serpin），位于染色体18q21.3。该基因家族的功能之一被认为是抑制肿瘤的血管生成、侵袭和转移。RT-PCR结果显示HEADPIN基因在30例口腔鳞癌中有17例（56.7%）表达下调，9例口腔鳞癌细胞系中有6例（66.7%）表达下调。此外，在用DNA去甲基化剂5-氮杂-2 '-脱氧胞苷处理后显示基因表达下调的6个OSCC衍生细胞系中的5个中诱导HEADPIN基因mRNA的恢复。因此，HEADPIN基因表达下调与口腔鳞癌的发生发展有关，HEADPIN基因甲基化是口腔鳞癌发生发展过程中HEADPIN基因失活的重要机制之一。