Exploratory study for identifying EMT-associated genes as novel therapeutics for lung cancer

鉴定 EMT 相关基因作为肺癌新疗法的探索性研究

• 批准号: 23591145
• 负责人: MITSUO Sato
• 金额: $ 3.33万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591145/
• 关键词: 肺癌; マイクロRNA; 上皮間葉細胞転換; EMT; 肺がん; 細胞周期; アポトーシス; 国際情報交換; 不死化正常気管支細胞; ｐ53; KRAS; EGFR; p53

We evaluated the potential of miR-221 and miR222 as novel therapeutics for lung cancer. These microRNAs are shown to induce epithelial to mesenchymal transition (EMT) in normal mammary epithelial cells. Upon introduction of miR-221 or miR222, immortalized normal human bronchial epithelial cells underwent morphological changes, suggestive of EMT, in association with expression changes in EMT-associated genes. miR-221 and miR222 promoted growth in several lung cancer cell lines but suppressed in other cell lines. Cell cycle and apoptosis analyses revealed that growth suppressive effects by miR-221 and miR-221 occur through S-phase arrest and/or apoptosis. These data suggested the potential of miR-221 and miR222 as novel therapeutics for lung cancer.

我们评估了miR-221和miR 222作为肺癌新疗法的潜力。 这些microRNA显示在正常乳腺上皮细胞中诱导上皮向间充质转化（EMT）。 在引入miR-221或miR-222后，永生化的正常人支气管上皮细胞经历了形态学变化，提示EMT，与EMT相关基因的表达变化相关。 miR-221和miR-222在几种肺癌细胞系中促进生长，但在其他细胞系中抑制生长。 细胞周期和凋亡分析显示，miR-221和miR-221的生长抑制作用通过S期阻滞和/或凋亡发生。 这些数据表明miR-221和miR 222作为肺癌新疗法的潜力。

项目成果

Human lung epithelial cells progressed to malignancy through specific oncogenic manipulations.

• DOI: 10.1158/1541-7786.mcr-12-0634-t
• 发表时间: 2013-06
• 期刊: Molecular cancer research : MCR
• 作者: Sato M;Larsen JE;Lee W;Sun H;Shames DS;Dalvi MP;Ramirez RD;Tang H;DiMaio JM;Gao B;Xie Y;Wistuba II;Gazdar AF;Shay JW;Minna JD
• 通讯作者: Minna JD

Transient but not stable ZEB1 knockdown dramatically inhibits growth of malignant pleural mesothelioma cells.

瞬态但不稳定的Zeb1敲低会大大抑制恶性胸膜间皮瘤细胞的生长。

• DOI: 10.1245/s10434-011-2142-0
• 发表时间: 2012-07
• 期刊: Annals of surgical oncology
• 影响因子: 3.7
• 作者: Horio M;Sato M;Takeyama Y;Elshazley M;Yamashita R;Hase T;Yoshida K;Usami N;Yokoi K;Sekido Y;Kondo M;Toyokuni S;Gazdar AF;Minna JD;Hasegawa Y
• 通讯作者: Hasegawa Y

Why, when and how to test for EGFR

为什么、何时以及如何检测 EGFR

• 发表时间: 2014
• 作者: Nakaji H;Petrova G;Matsumoto H;Iwata T;Ito I;Oguma T;Inoue H;Tajiri T;Nagasaki T;Kanemitsu Y;Niimi A;Mishima M.;佐藤光夫
• 通讯作者: 佐藤光夫

NeuroD1 regulation of migration accompanies the differential sensitivity of neuroendocrine carcinomas to TrkB inhibition.

• DOI: 10.1038/oncsis.2013.24
• 发表时间: 2013-08-19
• 期刊: ONCOGENESIS
• 影响因子: 6.2
• 作者: Osborne, J. K.;Larsen, J. E.;Gonzales, J. X.;Shames, D. S.;Sato, M.;Wistuba, I. I.;Girard, L.;Minna, J. D.;Cobb, M. H.
• 通讯作者: Cobb, M. H.

THE COMBINATION OF FIVE CHANGES (TELOMERASE, P16/RB BYPASS, P53 KNOCKDOWN, KRASV12, C-MYC) TOGETHERWITH SERUM-INDUCED EPITHELIAL MESENCHYMAL TRANSITION PROGRESSES NORMAL HUMAN BRONCHIAL EPITHELIAL CELLS TO FULL MALIGNANCY

五种变化（端粒酶、P16/RB 旁路、P53 敲低、KRASV12、C-MYC）与血清诱导的上皮间质转化的结合使正常人支气管上皮细胞发展为完全恶性肿瘤

• 发表时间: 2012
• 作者: Mitsuo Sato;Jill E. Larsen;Woochang Lee;David Shames;Ignacio I. Wistuba;Adi F. Gazdar3;Jerry W. Shay;John D. Minna;Masashi Kondo;Yoshinori Hasegawa
• 通讯作者: Yoshinori Hasegawa