Carcinogenesis Advance Access published online on May 22, 2003
Carcinogenesis, doi:10.1093/carcin/bgg089
© 2003 by Oxford University Press
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REVIEW
1 Laboratory of Chang-Jiang Scholar Endowment for Biomedical Sciences, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China; Department of Medicine, University of Colorado School of Medicine, CU Cancer Center, and Denver Health Medical Center, Denver, CO 80204, USA
* Corresponding author. E-mail: ming-hai.wang{at}uchsc.edu.
Received 20 January 2003
; revised 7 April 2003
; accepted 11 May 2003
The product of the RON (recepteur d'origine nantais) gene belongs to the MET proto-oncogene family, a distinct subfamily of receptor tyrosine kinases. The ligand of RON was identified as macrophage-stimulating protein (MSP), a member of the plasminogen-related growth factor family. RON is mainly expressed in cells of epithelial origin and is required for embryonic development. In vitro RON activation results in epithelial cell dissociation, migration, and matrix invasion, suggesting that RON might be involved in the pathogenesis of certain epithelial cancers in vivo. Indeed, recent studies have shown that RON expression is significantly altered in several primary human cancers, including those of the breast and colon. Truncation of the RON protein has also been found in primary tumors from the gastrointestinal tract. These alterations leads to constitutive activation of RON that causes cell transformation in vitro, induces neoplasm formation in athymic nude mice, and promotes tumor metastasis into the lung. Studies employing transgenic models further demonstrated that overexpression of RON in lung epithelial cells results in multiple tumor formation with features of large cell undifferentiated carcinoma. The oncogenic activities of RON are mediated by RON-transduced signals that promote unbalanced cell growth and transformation leading to tumor development. Thus, abnormal accumulation and activation of RON could play a critical role in vivo in the progression of certain malignant human epithelial cancers.
Receptor tyrosine kinase, Tumorigenesis, Invasiveness, Signal Transduction
Oncogenic and invasive potentials of human macrophage stimulating protein receptor, the RON receptor tyrosine kinase
2 Department of Medicine, University of Colorado School of Medicine, CU Cancer Center, and Denver Health Medical Center, Denver, CO 80204, USA
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