title: Differential expression of RON in small and non-small cell lung cancers.
abstract: RON is a MET related receptor tyrosine kinase (RTK) and its natural ligand is macrophage stimulating protein (MSP). RON plays a very important role in the regulation of inflammation. Several studies have previously reported overexpression of RON in a variety of cancers including lung and identified numerous RON alternate splice forms that very likely contribute to tumor growth and metastasis. Here, we have analyzed the expression of total RON protein as well as its kinase-active form (phospho-RON) in 175 archival lung tumor FFPE (formalin fixed paraffin embedded) samples that included non-small-cell lung cancer (NSCLC) and small cell lung cancer (SCLC), and their metastatic forms. The frequency and intensity of RON protein expression was much higher in lung tumors of neuroendocrine origin such as SCLC and in secondary tumors that metastasized to brain. In addition, the majority of the expressed RON protein was phospho-RON. We also identified 62, and 30 kDa isoforms of RON (GenBank accession numbers are JN689381 and JN689382) using RNA isolated from pooled lung cancer cell lines and RT-PCR. A majority of the NSCLC cell lines expressed a 150 kDa band that corresponded to the RON β chain and 120 kDa band in the panel of SCLC cell lines tested. RON was expressed on the cell surface in NSCLC cell lines. Finally, knock down of RON expression resulted in a significant loss in viability as well as motility in lung cancer cells suggesting that RON is a potential therapeutic target.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Rajani
authors.initials: R
authors.lastname: Kanteti
authors.forename: Soundararajan
authors.initials: S
authors.lastname: Krishnaswamy
authors.forename: Daniel
authors.initials: D
authors.lastname: Catenacci
authors.forename: Yi-Hung Carol
authors.initials: YH
authors.lastname: Tan
authors.forename: Essam
authors.initials: E
authors.lastname: EL-Hashani
authors.forename: Gustavo
authors.initials: G
authors.lastname: Cervantes
authors.forename: Aliya N
authors.initials: AN
authors.lastname: Husain
authors.forename: Maria
authors.initials: M
authors.lastname: Tretiakova
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Heather
authors.initials: H
authors.lastname: Huet
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D046888:Tissue Array Analysis; D014945:Wound Healing
chemical_list: D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases