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Targeted expression of the receptor tyrosine kinase RON in distal lung epithelial cells results in multiple tumor formation: oncogenic potential of RON in vivo

Oncogene volume 21, pages 6382–6386 (2002)Cite this article

Abstract

RON, a member of the MET proto-oncogene family, has been implicated in the progression of certain epithelial cancers. The purpose of this study was to determine the oncogenic potential of RON in vivo in lung epithelial cells. Transgenic mice were established using surfactant protein C promoter to express human RON in the distal lung epithelial cells. These mice were born normal but developed multiple lung tumors with distinct morphology and growth patterns. Tumors appeared as a single mass in the lung around 2 months of age and gradually developed into multiple nodules located mostly in the peripheral portions of the lung. A transition from early adenomas to later adenocarcinomas was observed. Morphologically, tumors were characterized as cuboidal epithelial cells with a type II cell phenotype, grew along the alveolar walls, and projected into the alveolar septa. RON was highly expressed and constitutively activated in tumors. These results indicate that overexpression of human wild-type RON causes the formation of lung tumors with unique biological characteristics in vivo. This model provides opportunities to study the role of RON in the pathogenesis of lung tumors and to elucidate the mechanisms underlying this distinct lung tumor.

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Acknowledgements

We thank Drs JA Whitsett (University of Cincinnati, Cincinnati, OH, USA) for the 3.7SPC/SV40 vector, G Singh (Department of Veterans Affairs Medical Center, Pittsburgh, PA, USA) for antibodies to CC10 and proSPC, and W Gunning (Medical College of Ohio, Toledo, OH, USA) for histological examination. We are indebted to Dr Y-S Ho for his kind help in the generation of the transgenic mice. This work was supported by NIH Grants RO1 AI43516 and CA91980 to M-H Wang.

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Authors and Affiliations

  1. Division of Pulmonary Sciences and Critical Care, Department of Medicine, University of Colorado School of Medicine, CU Cancer Center, and Denver Health Medical Center, Denver, 80204, Colorado, CO, USA

    Yi-Qing Chen, James H Fisher & Ming-Hai Wang

  2. Division of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China

    Yong-Qing Zhou

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  1. Yi-Qing Chen
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Correspondence to Ming-Hai Wang.

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Chen, YQ., Zhou, YQ., Fisher, J. et al. Targeted expression of the receptor tyrosine kinase RON in distal lung epithelial cells results in multiple tumor formation: oncogenic potential of RON in vivo. Oncogene 21, 6382–6386 (2002). https://doi.org/10.1038/sj.onc.1205783

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