Molecular mechanism of development and repression of lung tumor in OGG1 knockout mouse

OGG1基因敲除小鼠肺肿瘤发生和抑制的分子机制

• 批准号: 15590347
• 负责人: SAKUMI Kunihiko
• 金额: $ 2.24万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590347/
• 关键词: 8-oxoguanine; MTH1 gene; OGG1 gene; spontaneous tumorigenesis; lung

Using Mth1 and Ogg1 knockout mice, we evaluated the roles of these enzymes to prevent tumorigenesis and the accumulation of 8-oxoguanine(8-oxoG) in DNA. We found that lung adenoma/carcinoma spontaneously developed in Ogg1 knockout mice 1.5 years after birth in which 8-oxoG was found to accumulate in their genomes. The mean number of tumors/mouse was 0.71 for the Ogg1 knockout mice, which was five times higher than that observed in wild-type mice (0.14). Although the accumulation of 8-oxoG was also confirmed in the Ogg1,Mth1 double knockout mice, we found no tumor in the lungs of these mice. This observation suggests that Mth1 gene disruption resulted in a suppression of the tumorigenesis caused by an Ogg1 deficiency.We found an 8-oxoguanine accumulation-dependent expression pattern of specific genes using oligoDNA microarray analysis. Because 8-oxoguanine is localized at distinct regions on the chromosomes, 8-oxoguanine may affect directly on the gene expressions.

使用MTH1和OGG1基因敲除小鼠，我们评估了这些酶在DNA中预防肿瘤发生的作用和8-氧气（8-oxog）的积累。我们发现，出生后1.5年，在其基因组中发现8-oxog积聚在OGG1基因敲除小鼠中，肺腺瘤/癌自发发展。 OGG1敲除小鼠的肿瘤/小鼠的平均数量为0.71，比野生型小鼠观察到的小鼠高五倍（0.14）。尽管在OGG1（MTH1双基因敲除小鼠）中也证实了8-oxog的积累，但我们发现这些小鼠的肺中没有肿瘤。该观察结果表明，MTH1基因的破坏导致了由OGG1缺乏症引起的肿瘤发生的抑制。我们发现，使用寡素微阵列分析发现了特定基因的8-氧气积累依赖性表达模式。由于8-氧气鸟氨酸位于染色体上的不同区域，因此8-氧气鸟氨酸可能直接影响基因表达。

项目成果

MUTYH prevents OGG1 or APEX1 from inappropriately processing its substrate or reaction product with its C-terminal domain.

MUTYH 防止 OGG1 或 APEX1 以其 C 端结构域不当处理其底物或反应产物。

• 发表时间: 2004
• 期刊: Nucleic Acids Research 32(10)
• 作者: Tominaga Y;Ushijima Y;Tsuchimoto D;Mishima M;Shirakawa M;Hirano S;Sakumi K;Nakabeppu Y.
• 通讯作者: Nakabeppu Y.

The defense mechanisms in mammalian cells against oxidative damage in nucleic acids and their involvement in the suppression of mutagenesis and cell death

• DOI: 10.1080/10715760410001688348
• 发表时间: 2004-05-01
• 期刊: FREE RADICAL RESEARCH
• 影响因子: 3.3
• 作者: Nakabeppu, Y;Tsuchimoto, D;Sakumi, K
• 通讯作者: Sakumi, K

Ogg1 knockout mouse.

Ogg1 基因敲除小鼠。

• 发表时间: 2003
• 期刊: Bunshi Kokyukibyo 7(6)
• 作者: Sakumi K;Nakabeppu Y.
• 通讯作者: Nakabeppu Y.

MUTYH prevents OGG1 or APEX1 from inappropriately processing its substrate or reaction product with its C-terminal domain

MUTYH 防止 OGG1 或 APEX1 以其 C 端结构域不当处理其底物或反应产物

• 发表时间: 2004
• 期刊: Nucleic Acids Res. 32(10)
• 作者: Tominaga Y;Ushijima Y;Tsuchimoto D;Mishima M;Shirakawa M;Hirano;Sakumi K;Nakabeppu Y.
• 通讯作者: Nakabeppu Y.

Galectin-1beta, a natural monomeric form of galectin-1 lacking its six ainino-terminal residues promotes axonal regeneration but not cell death.

Galectin-1beta 是 Galectin-1 的天然单体形式，缺乏六个氨基末端残基，可促进轴突再生，但不会促进细胞死亡。

• 发表时间: 2004
• 期刊: Cell Death Differ. 11(10)
• 作者: Miura T;Takahashi M;Horie H;Kurushima H;Tsuchimoto D;Sakumi K;Nakabeppu Y
• 通讯作者: Nakabeppu Y