Identification of the genes involved in the tumorigenesis and spontaneous regression of neuroblastoma via array CGH analysis with model mice

通过模型小鼠阵列 CGH 分析鉴定参与神经母细胞瘤肿瘤发生和自发消退的基因

• 批准号: 22790311
• 负责人: KISHIDA Satoshi
• 金额: $ 2.58万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790311/
• 关键词: 神経芽腫; モデルマウス; CGHアレイ; Cited2; がん幹細胞; 神経芽種

We tried to identify the genes involved in the tumorigenesis and spontaneous regression of neuroblastoma via array CGH analysis with MYCN Tg mice, a model for neuroblastoma. For the purpose of evaluating the huge number of chromosomal aberrations, we set three parameters and calculated the scores. As a result, we identified the gene, Cited2, which is deleted in all 12 terminal tumors. Neuroblastoma in MYCN Tg mice turned out to be composed of two distinguishable populations in terms of the expression level of Cited2. The cells with low Cited2 expression showed strikingly higher tumorigenic ability compared to high ones. We also found that Cited2 affected the expression of other neuroblastoma-related transcription factors. In addition, although the cells with low Cited2 expression gave rise to high ones in vivo, the opposite never occurred. This result indicates the hierarchy that the low ones are superior to high ones. Taken together, the low expression of Cited2 might be the hallmark as cancer stem cells of neuroblastoma.

我们试图通过对MYCN Tg小鼠（一种神经母细胞瘤模型）的阵列CGH分析来鉴定与神经母细胞瘤的肿瘤发生和自发消退有关的基因。为了评估大量的染色体畸变，我们设置了三个参数并计算了分数。结果，我们鉴定出了在所有12个晚期肿瘤中缺失的基因Cited2。MYCN Tg小鼠中的神经母细胞瘤由两个可区分的群体组成，这两个群体在Cited2的表达水平方面是不同的。Cited2低表达细胞的致瘤能力明显高于高表达细胞。我们还发现Cited2影响了其他神经母细胞瘤相关转录因子的表达。此外，虽然Cited2低表达的细胞在体内产生高表达，但从未发生相反的情况。这一结果表明了低层次上级高层次。因此，Cited2的低表达可能是神经母细胞瘤肿瘤干细胞的标志。

项目成果

DRR1 is expressed in the developing nervous system and downregulated during neuroblastoma carcinogenesis

• DOI: 10.1016/j.bbrc.2010.03.085
• 发表时间: 2010-04-09
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Asano, Yoshizumi;Kishida, Satoshi;Kadomatsu, Kenji
• 通讯作者: Kadomatsu, Kenji

Midkine inhibits inducible regulatory T cell dififerentiation by suppressing the development of tolerogenic dendritic cells

Midkine 通过抑制耐受性树突状细胞的发育来抑制诱导性调节性 T 细胞分化

• 发表时间: 2012
• 期刊: Journal of immunology
• 影响因子: 4.4
• 作者: 井上純;白樺;河野辰幸;稲澤讓治;Yoshifumi Sonobe
• 通讯作者: Yoshifumi Sonobe

The Neuronal Differentiation Factor NeuroD1 Downregulates the Neuronal Repellent Factor Slit2 Expression and Promotes Cell Motility and Tumor Formation of Neuroblastoma

• DOI: 10.1158/0008-5472.can-10-3524
• 发表时间: 2011-04-15
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Huang, Peng;Kishida, Satoshi;Kadomatsu, Kenji
• 通讯作者: Kadomatsu, Kenji

The search for TICs- or malignancy-related genes in neuroblastoma model mice utilizing Next-Generation Sequencing

利用下一代测序在神经母细胞瘤模型小鼠中寻找 TIC 或恶性肿瘤相关基因

• 发表时间: 2011
• 作者: Inoue J;Misawa A;Tanaka Y;Ichinose S;Sugino Y;Hosoi H;Sugimoto T;Imoto I;Inazawa J;Satoshi Kishida;岸田聡
• 通讯作者: 岸田聡

Midkine Inhibits Inducible Regulatory T Cell Differentiation by Suppressing the Development of Tolerogenic Dendritic Cells

• DOI: 10.4049/jimmunol.1102346
• 发表时间: 2012-03-15
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Sonobe, Yoshifumi;Li, Hua;Suzumura, Akio
• 通讯作者: Suzumura, Akio