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Recepteur d’origine nantais(RON)belongs to a subfamily of receptor tyrosinekinases(RTK)with unique expression patterns and biological activities.RON isactivated by a serum-derived growth factor macrophage stimulating protein(MSP).The RON gene transcription is essential for embryonic development and critical inregulating certain physiological processes.Recent studies have indicated thataltered RON expression contributes significantly to cancer progression andmalignancy.In primary tumors,such as colon and breast cancers,overexpressionof RON exists in large numbers and is often accompanied by the generation ofdifferent splicing variants.These RON variants direct a unique program thatcontrols cell transformation,growth,migration,and invasion,indicating that al-tered RON expression has the ability to regulate motile/invasive phenotypes.These activities were also seen in transgenic mice,in which targeted expression ofRON in lung epithelial cells resulted in numerous tumors with pathological fea-tures of human bronchioloalveolar carcinoma.Thus,abnormal RON activation isa pathogenic factor that transduces oncogenic signals leading to uncontrolledcell growth and subsequent malignant transformation.Considering these facts,RON and its variants can be considered as potential targets for therapeuticintervention.Experiments using small interfering RNA and neutralizing mono-clonal antibodies demonstrated that suppressing RON expression and activationdecreases cancer cell proliferation,increases apoptotic death,prevents tumorformation in nude mice,and reduces malignant phenotypes.Thus,blocking RONexpression and activation has clinical significance in reversing malignant pheno-types and controlling tumor growth.
Recepteur d’origine nantais (RON) belongs to a subfamily of receptor tyrosinekinases (RTK) with unique expression patterns and biological activities. ON isactivated by a serum-derived growth factor macrophage stimulating protein (MSP). The RON gene transcription is essential for embryonic development and critical inregulating certain physiological processes. Recent studies have indicated that localized RON expression contributes significantly to cancer progression and malignancy. In primary tumors, such as colon and breast cancers, overexpression of RON exists in large numbers and is often accompanied by the generation of different splicing variants. These RON variants direct a unique program thatcontrols cell transformation, growth, migration, and invasion, indicating that al-tered RON expression has the ability to regulate motile / invasive phenotypes. These activities were also seen in transgenic mice, in which targeted expression of Ron in lung epithelial cells resulted in numerous tumors with pathologica l fea-tures of human bronchioloalveolar carcinoma. Thus, abnormal RON activation isa pathogenic factor that transduces oncogenic signals leading to uncontrolled cell growth and subsequent malignant transformation. C on c ideological these facts, RON and its variants can be considered as potential targets for therapeutic intervention. Experiments using small interfering RNA and neutralizing mono-clonal antibodies to suppress the expression of RON expression and activation mutations in cancer cell proliferation, elevational apoptotic death, prevents tumorformation in nude mice, and reduces malignant phenotypes. Thus, blocking RONexpression and activation has clinical significance in reversing malignant pheno-types and controlling tumor growth.