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.

在2006年，我们确定了舌头发育异常，乳头状瘤，乳头状瘤和鳞状细胞癌的p14，p16，APC，GSTP和细胞周期蛋白D2基因的DNA甲基化谱，由4-硝基喹啉1-氧化物在Rash2小鼠中诱导。在舌癌发生过程中，我们观察到这些基因中的甲基化谱。尤其是在致癌过程中APC和细胞周期蛋白D2的高甲基化率升高。甲基化特异性PCR。 p16，p15，p14，atm和GSTP1的高甲基化速率为42％，58％，37％，35％，35％，24％，在GSTP-PS阳性异常增生和31％，29％，31​​％，28％，28％，10％，10％，10％，10％，10％。另外，我们观察到，p16，p15，p14，att和GSTP1的高甲基化速率为50％，67％，52％，68％，68％，40％，40％，33％，33％，31％，31％，40％，40％，24％，24％，19％，19％，19％，19％，19％，19％，19％，19％，19％，19％。我们的发现表明，GST-P的发育异常可能是舌性恶性肿瘤的直接前体病变，并且某些功能性细胞生长和凋亡的基因中的过度甲基化以及与排毒有关的高甲基化涉及舌头致癌。

项目成果

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.

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

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

An animal model for the rapid mduction of tongue neoplasms in human c-Ha-ras proto-oncogene transgenic rats by 4-nitroquinofine 1-oxide:Its potential use for preclinical chemoprevention studies

4-硝基喹诺芬1-氧化物快速诱导人c-Ha-ras原癌基因转基因大鼠舌肿瘤的动物模型：其在临床前化学预防研究中的潜在用途

• 发表时间: 2006
• 期刊: Carcinogenesis 27
• 作者: Suzuki;R.
• 通讯作者: R.