Implications of EPHB6, EFNB2, and EFNB3 expressions in human neuroblastoma Journal Article


Authors: Tang, X. X.; Zhao, H.; Robinson, M. E.; Cohen, B.; Cnaan, A.; London, W.; Cohn, S. L.; Cheung, N. K. V.; Brodeur, G. M.; Evans, A. E.; Ikegaki, N.
Article Title: Implications of EPHB6, EFNB2, and EFNB3 expressions in human neuroblastoma
Abstract: Neuroblastoma (NB) is a common pediatric tumor that exhibits a wide range of biological and clinical heterogeneity. EPH (erythropoietin-producing hepatoma amplified sequence) family receptor tyrosine kinases and ligand ephrins play pivotal roles in neural and cardiovascular development. High-level expression of transcripts encoding EPHB6 receptors (EPHB6) and its ligands ephrin-B2 and ephrin-B3 (EFNB2, EFNB3) is associated with low-stage NB (stages 1, 2, and 4S) and high TrkA expression. In this study, we showed that EFNB2 and TrkA expressions were associated with both tumor stage and age, whereas EPHB6 and EFNB3 expressions were solely associated with tumor stage, suggesting that these genes were expressed in distinct subsets of NB. Kaplan-Meier and Cox regression analyses revealed that high-level expression of EPHB6, EFNB2, and EFNB3 predicted favorable NB outcome (P < 0.005), and their expression combined with TrkA expression predicted the disease outcome more accurately than each variable alone (P < 0.00005). Interestingly, if any one of the four genes (EPHB6, EFNB2, EFNB3, or TrkA) was expressed at high levels in NB, the patient survival was excellent (>90%). To address whether a good disease outcome of NB was a consequence of high-level expression of a 'favorable NB gene,' we examined the effect of EPHB6 on NB cell lines. Transfection of EPHB6 cDNA into IMR5 and SY5Y expressing little endogenous EPHB6 resulted in inhibition of their clonogenicity in culture. Furthermore, transfection of EPHB6 suppressed the tumorigenicity of SY5Y in a mouse xenograft model, demonstrating that high-level expressions of favorable NB genes, such as EPHB6, can in fact suppress malignant phenotype of unfavorable NB.
Keywords: cancer survival; controlled study; human tissue; child, preschool; survival analysis; cancer growth; nonhuman; cancer staging; brain neoplasms; mouse; phenotype; animal; mice; gene expression; tumor markers, biological; animal experiment; membrane proteins; age; gene expression regulation, neoplastic; infant; neuroblastoma; carcinogenicity; ligand; predictive value of tests; receptor protein-tyrosine kinases; regression analysis; receptors, eph family; ephrin; ephrin-b2; prognosis; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; receptor, ephb4
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 97
Issue: 20
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2000-09-26
Start Page: 10936
End Page: 10941
Language: English
PUBMED: 10984508
PROVIDER: scopus
PMCID: PMC27127
DOI: 10.1073/pnas.190123297
DOI/URL:
Notes: Export Date: 18 November 2015 -- Source: Scopus
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  1. Nai-Kong Cheung
    650 Cheung