Mouse model for ROS1-rearranged lung cancer.
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-ROS...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3572153?pdf=render |
| _version_ | 1818179638221864960 |
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| author | Yasuhito Arai Yasushi Totoki Hiroyuki Takahashi Hiromi Nakamura Natsuko Hama Takashi Kohno Koji Tsuta Akihiko Yoshida Hisao Asamura Michihiro Mutoh Fumie Hosoda Hitoshi Tsuda Tatsuhiro Shibata |
| author_facet | Yasuhito Arai Yasushi Totoki Hiroyuki Takahashi Hiromi Nakamura Natsuko Hama Takashi Kohno Koji Tsuta Akihiko Yoshida Hisao Asamura Michihiro Mutoh Fumie Hosoda Hitoshi Tsuda Tatsuhiro Shibata |
| author_sort | Yasuhito Arai |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T21:07:03Z |
| format | Article |
| id | doaj.art-b099cf1e4db349c6bc3ca70234652253 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T21:07:03Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b099cf1e4db349c6bc3ca702346522532022-12-22T00:50:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5601010.1371/journal.pone.0056010Mouse model for ROS1-rearranged lung cancer.Yasuhito AraiYasushi TotokiHiroyuki TakahashiHiromi NakamuraNatsuko HamaTakashi KohnoKoji TsutaAkihiko YoshidaHisao AsamuraMichihiro MutohFumie HosodaHitoshi TsudaTatsuhiro ShibataGenetic 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.http://europepmc.org/articles/PMC3572153?pdf=render |
| spellingShingle | Yasuhito Arai Yasushi Totoki Hiroyuki Takahashi Hiromi Nakamura Natsuko Hama Takashi Kohno Koji Tsuta Akihiko Yoshida Hisao Asamura Michihiro Mutoh Fumie Hosoda Hitoshi Tsuda Tatsuhiro Shibata Mouse model for ROS1-rearranged lung cancer. PLoS ONE |
| title | Mouse model for ROS1-rearranged lung cancer. |
| title_full | Mouse model for ROS1-rearranged lung cancer. |
| title_fullStr | Mouse model for ROS1-rearranged lung cancer. |
| title_full_unstemmed | Mouse model for ROS1-rearranged lung cancer. |
| title_short | Mouse model for ROS1-rearranged lung cancer. |
| title_sort | mouse model for ros1 rearranged lung cancer |
| url | http://europepmc.org/articles/PMC3572153?pdf=render |
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