Identification of downstream regulatory factor in RET signaling pathway and its application to cancer treatment

RET信号通路下游调控因子的鉴定及其在癌症治疗中的应用

• 批准号: 20590412
• 负责人: ICHIHARA Masatoshi
• 金额: $ 3万
• 依托单位: Chubu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590412/
• 关键词: RET; チロシンキナーゼ; アイソフォーム; DNAマイクロアレイ; isoform; LC/MS; LC; MS

Ret tyrosine kinase (RET) plays critical roles in embryonic development as well as oncogenesis. RET is mainly expressed as two isoforms, RET51 and RET9, which have different C-terminal ends generated through alternative splicing , whereas previous studies show that RET9 is indispensable for nephrogenesis and enteric neurogenesis. We found remarkable increase of tyrosine- phosphorylated proteins in the cells after inducible expression of RET9 in MEF3T3 cells. We demonstrated that 261 genes were differentially expressed under inducible expression of either RET51 or RET9 by gene expression profiling. Ingenuity pathway analysis revealed that gene expression-related genes, including transcription factors, were enriched in these differentially expressed genes. Next we tried to identify differentially binding protein to RET between RET51 and RET9 using LC/MS, but we failed to find such candidate proteins, accounting for different function between RET51 and RET9.

RET酪氨酸激酶(RET)在胚胎发育和肿瘤发生中起重要作用。RET主要表达为RET51和RET9两种异构体，它们通过选择性剪接产生不同的C末端，而先前的研究表明RET9在肾脏发生和肠神经发生中是不可或缺的。我们发现，在MEF3T3细胞中诱导表达RET9后，细胞中的酪氨酸磷酸化蛋白显著增加。我们通过基因表达谱证明，在RET51或RET9的诱导表达下，有261个基因有差异表达。独创性途径分析表明，基因表达相关基因，包括转录因子，在这些差异表达的基因中得到了丰富。接下来，我们试图用LC/MS鉴定RET51和RET9中与RET结合的差异蛋白，但我们没有找到这样的候选蛋白，这是RET51和RET9功能不同的原因。

项目成果

Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cells.

• DOI: 10.1091/mbc.e10-08-0724
• 发表时间: 2011-03-15
• 期刊: Molecular biology of the cell
• 影响因子: 3.3
• 作者: Matsushita E;Asai N;Enomoto A;Kawamoto Y;Kato T;Mii S;Maeda K;Shibata R;Hattori S;Hagikura M;Takahashi K;Sokabe M;Murakumo Y;Murohara T;Takahashi M
• 通讯作者: Takahashi M

Analysis of glial cell line-derived neurotrophic factor-inducible zinc finger protein 1 expression in human diseased kidney.

• DOI: 10.1016/j.humpath.2010.09.015
• 发表时间: 2011-06
• 期刊: Human pathology
• 影响因子: 3.3
• 作者: Shoji Saito;Y. Murakumo;T. Tsuzuki;Atsushi Dambara;Takuya Kato;A. Enomoto;N. Asai;S. Maruyama;S. Matsuo;Masahide Takahashi

beta-Catenin signaling regulates the timing of cell differentiation in mouse retinal progenitor cells.

β-连环蛋白信号传导调节小鼠视网膜祖细胞的细胞分化时间。

• 发表时间: 2011
• 期刊: Mol Cell Neurosci. 46
• 作者: Ouchi Y;Baba Y;Koso H;Taketo MM;Iwamoto T;Aburatani H;Watanabe S
• 通讯作者: Watanabe S

膀胱癌におけるCD109発現の臨床病理学的特徴との関連性の検討

膀胱癌CD109表达与临床病理特征的关系探讨

• 发表时间: 2010
• 作者: 伊藤智広;藤田泰典;伊藤美佳子;増田章男;市原正智;小島俊男;野澤義則;大野欽司;伊藤雅史;伊藤智広;市原正智;祖父江沙矢加;山本純矢;大内靖夫;喬善楼;Murakumo Y;三井伸二;村雲芳樹;萩倉美奈子
• 通讯作者: 萩倉美奈子

口腔癌におけるCD109の発現

CD109在口腔癌中的表达

• 发表时间: 2008
• 作者: 萩原純孝;村雲芳樹;重富俊雄;光藤健司;藤内祝;上田実;高橋雅英
• 通讯作者: 高橋雅英