Methylation of GST-P-positive tongue preneoplastic lesions

GST-P 阳性舌癌前病变的甲基化

• 批准号: 18592076
• 负责人: TANAKA Takuji
• 金额: $ 2.39万
• 依托单位: Kanazawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18592076/
• 关键词: Cancer; Genome; Cell and Tissue; Animal; Oral cavity

In 2006, we determined DNA methyaltion profiles of p14, p16, Apc, GSTP, and cyclin D2 genes in tongue dysplasias, papillomas, and squamous cell carcinomas induced by 4-nitroquinoline 1-oxide in rasH2 mice. We observed different methylation profiles in these genes during tongue carcinogenesis. Especially the rates of hypermethylation of Apc and cyclin D2 increased during the carcinogenesis.In 2007, we investigated the presence of mythylation in the tongue dysplastic lesions (n=50) and squamous cell carcinoma(n=24) that are positive (25 dysplasias and 12 carcinomas) or negative (25 dysplasias and 12 carcinomas) for GSTP immunohistochemistry using methylation-specific PCR. The rates of hypermethylation of p16, p15, p14, ATM, and GSTP1 were 42%, 58%, 37%, 35%, 24% in the GST-P-positive dysplasia and 31%, 29%, 31%, 28%, 10% in the GSTP-negative dysplasia. Also, we observed that the rates of hypermethylation of p16, p15, p14, ATM, and GSTP1 were 50%, 67%, 52%, 68%, 40% in the GST-P-positive carcinoma and 33%, 31%, 40%, 24%, 19% in the GSTP-negative carcinoma. Our findings suggest that dysplasias positive for GST-P might be direct precursor lesions for tongue malignancy and that hypermethylation in certain genes functioning cell growth and apoptosis and those related to detoxification is involved in tongue carcinogenesis.

2006年，我们测定了p14、p16、APC、GSTP和细胞周期蛋白D2基因在4-硝基喹啉1-氧化物诱导的rasH2小鼠舌癌、乳头状瘤和鳞状细胞癌中的DNA甲基化情况。我们观察到这些基因在舌癌发生过程中的不同甲基化状态。2007年，我们采用甲基化特异性聚合酶链式反应技术对50例舌癌组织和24例鳞状细胞癌组织中APC和Cyclin D2的甲基化情况进行了研究。在GST-P阳性的异型增生中，p16、p15、p14、ATM和GSTP1的甲基化率分别为42%、58%、37%、35%和24%，在GSTP阴性的异型增生中分别为31%、29%、31%、28%和10%。在GST-P阳性的癌组织中，p16、p15、p14、ATM和GSTP1的甲基化率分别为50%、67%、52%、68%和40%，在GSTP阴性的癌组织中分别为33%、31%、40%、24%和19%。我们的研究结果提示，GST-P阳性的异型增生可能是舌癌的直接前驱病变，某些功能基因的甲基化、细胞生长和细胞凋亡以及与解毒相关的基因高甲基化参与了舌癌的发生。

项目成果

A novel rasH2 mouse carcinogenesis model that is highly susceptible to 4-NQO-induced tongue and esophageal carcinogenesis is useful for preclinical chemoprevention studies

• DOI: 10.1093/carcin/bgm225
• 发表时间: 2008-02-01
• 期刊: CARCINOGENESIS
• 影响因子: 4.7
• 作者: Miyamoto, Shingo;Yasui, Yumiko;Tanaka, Takuji
• 通讯作者: Tanaka, Takuji

Dextran sodium sulfate promotes colorectal carcinogenesis in Apc mice : Inflammation stimuli by dextran sodium sulfate resulfes in development of multiple colonic neoplasms.

右旋糖酐硫酸钠促进 Apc 小鼠结直肠癌的发生：右旋糖酐硫酸钠的炎症刺激导致多发性结肠肿瘤的发展。

• 发表时间: 2006
• 期刊: Int.J.Cancer 118・1
• 作者: Takuji Tanaka;et al.
• 通讯作者: et al.

Potent inhibitory effect of trans9, trans 11 isomer of conjugated linoleic acid on the growth of human colon cancer cells

• DOI: 10.1016/j.jnutbio.2006.01.007
• 发表时间: 2006-12-01
• 期刊: JOURNAL OF NUTRITIONAL BIOCHEMISTRY
• 影响因子: 5.6
• 作者: Beppu, Fumiaki;Hosokawa, Masashi;Miyashita, Kazuo
• 通讯作者: Miyashita, Kazuo

A novel rasH2 mouse carcinogenesis model that is highly susceptible to 4-NQO-1 nduced tongue and esophageal carcinogenesis is useful for preclinical chemoprevention studies.

一种新型 rasH2 小鼠致癌模型，对 4-NQO-1 诱导的舌癌和食管癌高度敏感，可用于临床前化学预防研究。

• 发表时间: 2008
• 期刊: Carcinogenesis 29
• 作者: Miyamoto;S.
• 通讯作者: S.

Dietary pitavastatin inhibits 4-nitroquinoline-1-oxide-induced carcinogenesis in the upper-digestive organs of rasH2 mice.

膳食匹伐他汀可抑制 rasH2 小鼠上消化器官中 4-硝基喹啉-1-氧化物诱导的癌变。

• 发表时间: 2007
• 作者: Kim Mihye;Yumiko Yasui;Shingo Miyamoto;Shigeyuki Sugie;Akira Murakami;Rikako Ishigamori-Suzuki;Takuji Tanaka
• 通讯作者: Takuji Tanaka