Molecular mechanisms of epigenetic alterations in gastrointestinal cancer and application to diagnosis and therapy

胃肠癌表观遗传改变的分子机制及其在诊断和治疗中的应用

• 批准号: 17109008
• 负责人: IMAI Kohzoh
• 金额: $ 70.89万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17109008/
• 关键词: DNAメチル化; エピジェネティクス; ヒストン修飾; 個別化医療; 遺伝子診断; 分子標的治療; メチル化; 消化器癌; 遺伝子発現; 腫瘍マーカー; 分子標的

Molecular mechanisms how this epigenetic alterations contribute to development of tumors remains to be determined. DNA methylation also leads to silencing of genes involved in cell signaling, which in turn leads to dysregulation of the oncogenic signaling such as Ras, WNT, and microRNA. We found that epigenetic inactivation of IGFBP7 plays a critical role in escaping senescence in CIMP positive colorectal cancers. We also found that epigenetic information can be used to detect cancer cells from colorectal mucosal solution.

这种表观遗传改变如何促进肿瘤发展的分子机制仍有待确定。 DNA 甲基化还会导致参与细胞信号传导的基因沉默，进而导致 Ras、WNT 和 microRNA 等致癌信号传导失调。我们发现 IGFBP7 的表观遗传失活在 CIMP 阳性结直肠癌逃避衰老中发挥着关键作用。我们还发现表观遗传信息可用于检测结直肠粘膜溶液中的癌细胞。

项目成果

DNA hypermethylation contributes incomplete synthesis of carbohydrate determinants in gastrointestinal cancer.

DNA 高甲基化导致胃肠道癌症中碳水化合物决定簇的不完全合成。

• 发表时间: 2008
• 期刊: Gastroenterol 135
• 作者: Kawamura YI;Toyota M;Kawashima R;Hagiwara T;Suzuki H;Imai K;Shinomura Y;Tokino T;Kannagi R;Dohi T
• 通讯作者: Dohi T

Gene amplification and overexpression of PRDM14 in breast cancer

乳腺癌中 PRDM14 的基因扩增和过表达

• 发表时间: 2007
• 期刊: Cancer Res 67
• 作者: Nishikawa N;Toyota M;Suzuki H;Homma T;Fujikane T;Ohmura T;Nishidate T;Ohe-Toyota M;Maruyama R;Sonoda T;Sasaki Y;Urano T;Imai K;Hirata K;Tokino T
• 通讯作者: Tokino T

Genetic, epigenetic and clinicopathological features of gastric cancers with CpG island methylator phenotype and an association with Epstein-Barr virus.

具有 CpG 岛甲基化表型且与 Epstein-Barr 病毒相关的胃癌的遗传、表观遗传和临床病理学特征。

• 发表时间: 2006
• 期刊: Cancer 106
• 作者: Kusano M;Toyota M;Suzuki H;Akino K;Aoki F;Fujita M;Hosokawa M;Shinomura Y;Imai K;Tokino T
• 通讯作者: Tokino T

2-methoxywstradiol, an endogenous mammalian metabolite, radiosensitizes colon carcinoma cells through c-Jun NH2-terminal kinase activation.

2-methoxywstradiol 是一种内源性哺乳动物代谢物，通过 c-Jun NH2 末端激酶激活使结肠癌细胞放射增敏。

• 发表时间: 2006
• 期刊: Clin Cancer Res 12・21
• 作者: Takae Y;Nishikawa T;Amagai M;柳瀬 敏彦;Zou H et al.
• 通讯作者: Zou H et al.

A Single Recombinant Adenovirus Expressing p53 and p21-targeting Artificial microRNAs Efficiently Induces Apoptosis in Human Cancer Cells

• DOI: 10.1158/1078-0432.ccr-08-2396
• 发表时间: 2009-06-01
• 期刊: CLINICAL CANCER RESEARCH
• 影响因子: 11.5
• 作者: Idogawa, Masashi;Sasaki, Yasushi;Tokino, Takashi
• 通讯作者: Tokino, Takashi