Mouse model for ROS1-rearranged lung cancer.
Mouse model for ROS1-rearranged lung cancer.
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DOI：
10.1371/journal.pone.0056010
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shibata T
中科院分区：
文献类型：
--
作者：
Arai Y;Totoki Y;Takahashi H;Nakamura H;Hama N;Kohno T;Tsuta K;Yoshida A;Asamura H;Mutoh M;Hosoda F;Tsuda H;Shibata T
ROS1受体酪氨酸激酶的遗传重排最近被确定为人类非小细胞肺癌（NSCLC）的独特分子特征。然而，ROS1融合基因诱导肺癌的直接证据仍有待证实。本研究表明EZR-ROS1在携带融合基因的NSCLC的肿瘤发生中起重要作用。在4例女性肺腺癌患者中检测到EZR-ROS1。其中三人从不吸烟。6q22-q25的间质性缺失导致基因融合。融合激酶在NIH3T3细胞中的表达诱导体外非锚定生长和裸鼠皮下肿瘤。这种转化能力归因于它的激酶活性。ALK/MET/ROS1激酶抑制剂克唑替尼抑制融合诱导的NIH3T3细胞不依赖锚定的生长。最重要的是，在肺泡上皮细胞中特异性表达EZR-ROS1的转基因小鼠系在幼年时双肺出现多发腺癌结节。这些数据表明EZR-ROS1是人类非小细胞肺癌的关键癌基因，该动物模型可以为探索ros1重排肺癌的治疗药物提供价值。
Genetic rearrangement of the ROS1 receptor tyrosine kinase was recently identified as a distinct molecular signature for human non-small cell lung cancer (NSCLC). However, direct evidence of lung carcinogenesis induced by ROS1 fusion genes remains to be verified. The present study shows that EZR-ROS1 plays an essential role in the oncogenesis of NSCLC harboring the fusion gene. EZR-ROS1 was identified in four female patients of lung adenocarcinoma. Three of them were never smokers. Interstitial deletion of 6q22–q25 resulted in gene fusion. Expression of the fusion kinase in NIH3T3 cells induced anchorage-independent growth in vitro, and subcutaneous tumors in nude mice. This transforming ability was attributable to its kinase activity. The ALK/MET/ROS1 kinase inhibitor, crizotinib, suppressed fusion-induced anchorage-independent growth of NIH3T3 cells. Most importantly, established transgenic mouse lines specifically expressing EZR-ROS1 in lung alveolar epithelial cells developed multiple adenocarcinoma nodules in both lungs at an early age. These data suggest that the EZR-ROS1 is a pivotal oncogene in human NSCLC, and that this animal model could be valuable for exploring therapeutic agents against ROS1-rearranged lung cancer.
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DOI：
10.1158/1078-0432.ccr-12-0550
发表时间：
2012-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Davies KD;Le AT;Theodoro MF;Skokan MC;Aisner DL;Berge EM;Terracciano LM;Cappuzzo F;Incarbone M;Roncalli M;Alloisio M;Santoro A;Camidge DR;Varella-Garcia M;Doebele RC
通讯作者：
Doebele RC
影响因子：
3.7
作者：
Birch AH;Arcand SL;Oros KK;Rahimi K;Watters AK;Provencher D;Greenwood CM;Mes-Masson AM;Tonin PN
通讯作者：
Tonin PN
癌症中的酪氨酸激酶基因融合：将机制转化为靶向疗法。
影响因子：
5.3
作者：
Medves S;Demoulin JB
通讯作者：
Demoulin JB
影响因子：
3.7
作者：
Gu TL;Deng X;Huang F;Tucker M;Crosby K;Rimkunas V;Wang Y;Deng G;Zhu L;Tan Z;Hu Y;Wu C;Nardone J;MacNeill J;Ren J;Reeves C;Innocenti G;Norris B;Yuan J;Yu J;Haack H;Shen B;Peng C;Li H;Zhou X;Liu X;Rush J;Comb MJ
通讯作者：
Comb MJ
影响因子：
64.5
作者：
Govindan R;Ding L;Griffith M;Subramanian J;Dees ND;Kanchi KL;Maher CA;Fulton R;Fulton L;Wallis J;Chen K;Walker J;McDonald S;Bose R;Ornitz D;Xiong D;You M;Dooling DJ;Watson M;Mardis ER;Wilson RK
通讯作者：
Wilson RK