Role of EMT and growth factor cascade in development and cancer.

EMT 和生长因子级联在发育和癌症中的作用。

• 批准号: 20390096
• 负责人: YAMADA Gen
• 金额: $ 12.56万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-20390096/
• 关键词: 上皮間葉転換; EMT; 細胞増殖因子; 癌; 発生; Wnt; 遺伝子; 発生・分化; 泌尿生殖系; 外生殖器; ヘッジホッグ; Bmp(骨形成因子); Wntシグナル; 間葉; 平滑筋; 細胞系譜; ノギン(noggin)

We investigated the role of growth factor cascade and EMT (Epithelia Msenchyme Transition) during development and early oncogenic processes. During this research period, we published more than Development2、Endocrinology4、Molecular Endcrinology1、COGD1 papers. During skin development, we found abnormal Wnt/β catein signaling leads to skin hyperplasia. The phenotype can be studied more in relation to BCC. In such pathological condition, integration of Bmp-hedgehog signal transduction was also incorporated. During cloaca development, we investigated the role of growth factor signals and we found abnormal hedgehog and Wnt/β catein signal altered cloacal epithelial development. During the course of MD and female reproductive tract development, we investigated the role of Wnt/β catein cascade. We also found abnormal gain-of-function of Wnt/b catein signal leads to uterine gland (UG) hyperplasia and found such dysregulation in human endometorial hyperplasia samples. Thus, our project suggested a link of development and pathogenesis in terms of growth factor cascade.

我们研究了生长因子级联和上皮间质转化（EMT）在发育和早期致癌过程中的作用。在此研究期间，共发表《发育》、《内分泌学》、《分子内分泌学》、《COGD1》等多篇论文。在皮肤发育过程中，我们发现Wnt/β酪蛋白信号异常导致皮肤增生。表型可以更多地研究与BCC的关系。在这种病理状态下，Bmp-hedgehog信号转导的整合也被纳入。在泄殖腔发育过程中，我们研究了生长因子信号的作用，发现异常的hedgehog和Wnt/β catein信号改变了泄殖腔上皮的发育。在MD和女性生殖道发育过程中，我们研究了Wnt/β酪蛋白级联的作用。我们还发现Wnt/b酪蛋白信号的异常功能获得导致子宫腺（UG）增生，并在人子宫内膜增生样本中发现了这种异常。因此，我们的项目提出了生长因子级联的发展和发病机制的联系。

项目成果

Prostate expression of endothelins and their receptors in rat growth.

大鼠生长中内皮素及其受体的前列腺表达。

• 发表时间: 2008
• 期刊: Reprod Fertil Dev. 20
• 作者: Wada;Y.
• 通讯作者: Y.

Signaling pathways for external genitalia development., Gordon Research Conferences.

外生殖器发育的信号通路。戈登研究会议。

• 发表时间: 2010
• 作者: Makino H;Toyoda M;Matsumoto K;Saito H;Nishino K;Fukawatase Y;Machida M;Akutsu H;Uyama T;Miyagawa Y;Okita H;Kiyokawa N;Fujino T;Ishikawa Y;Nakamura T;Umezawa A;山田源
• 通讯作者: 山田源

Signaling pathways for external genitalia development.

外生殖器发育的信号通路。

• 发表时间: 2010
• 作者: Satoh Y;Hoshi R;Horai T;Okumura S;Nakagawa K;Ishikawa Y;Miyata S;Gen Yamada
• 通讯作者: Gen Yamada

生殖器官発生の解明Regulation of sexual dimorphism : Coordinated urogenital/reproductive organ formation

性二态性的调节：协调泌尿生殖/生殖器官的形成

• 发表时间: 2010
• 作者: Hanyu A;Kojima K;Hatake K;Nomura K;Murayama H;Ishikawa Y;Miyata S;Ushijima M;Matsuura M;Ogata E;Miyazawa K;Imamura T;中村裕,石川雄一;山田源
• 通讯作者: 山田源

A model for the development of sexual dimorphism : Wnt signal mediated external genitalia masculinization

性二态性发展模型：Wnt信号介导的外生殖器男性化

• 发表时间: 2010
• 作者: Takeuchi K;Ishikawa Y;et al.;Gen Yamada
• 通讯作者: Gen Yamada