PMID- 23999075 OWN - NLM STAT- MEDLINE DCOM- 20140616 LR - 20211021 IS - 1530-0447 (Electronic) IS - 0031-3998 (Print) IS - 0031-3998 (Linking) VI - 74 IP - 5 DP - 2013 Nov TI - Kidins220/ARMS is expressed in neuroblastoma tumors and stabilizes neurotrophic signaling in a human neuroblastoma cell line. PG - 517-24 LID - 10.1038/pr.2013.146 [doi] AB - BACKGROUND: Neurotrophic signaling is an important factor in the survival of developing neurons, and the expression of neurotrophic receptors correlates with prognosis in neuroblastoma. Kinase D-interacting substrate of 220 kDa (Kidins220) associates with neurotrophic receptors and stabilizes them, but the expression and function of Kidins220 in neuroblastoma are unknown. METHODS: We study Kidins220 expression in human neuroblastoma cell lines and tumor samples by western blotting and microarray analyses. We determine the functional consequences of downregulation of Kidins220 for response of cell lines to oxidative stress, chemotherapeutic treatment, and neurotrophins using small interfering RNA silencing and by measuring cell survival, signaling, and migration. RESULTS: Kidins220 is expressed in all neuroblastoma tumors and cell lines studied. Downregulation of Kidins220 leads to attenuation of nerve growth factor (NGF)-induced, but not brain-derived neurotrophic factor (BDNF)-induced, MAPK signaling. However, downregulation of Kidins220 does not alter the response to chemotherapeutic drugs or oxidative stress or affect cellular motility. CONCLUSION: Kidins220 is expressed in neuroblastoma tumors and stabilizes NGF-induced, but not BDNF-induced, survival signaling in neuroblastoma cell lines. FAU - Rogers, Danny A AU - Rogers DA AD - 1] Department of Pediatrics, University of Rochester Medical Center, Rochester, New York [2] Department of Neurology, University of Rochester Medical Center, Rochester, New York [3] Department of Neurobiology and Anatomy, University of Rochester Medical Center, Rochester, New York. FAU - Schor, Nina F AU - Schor NF LA - eng GR - R01 CA074289/CA/NCI NIH HHS/United States GR - R01 NS038569/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130902 PL - United States TA - Pediatr Res JT - Pediatric research JID - 0100714 RN - 0 (KIDINS220 protein, human) RN - 0 (Membrane Proteins) RN - 0 (Nerve Growth Factors) RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA, Small Interfering) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Blotting, Western MH - Cell Line, Tumor MH - Cell Movement MH - Cell Survival MH - Gene Expression Regulation, Neoplastic/*genetics MH - Humans MH - Hydrogen Peroxide MH - Membrane Proteins/genetics/*metabolism MH - Microarray Analysis MH - Mitogen-Activated Protein Kinases/*metabolism MH - Nerve Growth Factors/*metabolism MH - Nerve Tissue Proteins/genetics/*metabolism MH - Neuroblastoma/genetics/*metabolism MH - Oxidative Stress/genetics/physiology MH - RNA Interference MH - RNA, Small Interfering/genetics MH - Signal Transduction/genetics/*physiology PMC - PMC3968798 MID - NIHMS548702 EDAT- 2013/09/04 06:00 MHDA- 2014/06/17 06:00 PMCR- 2014/05/01 CRDT- 2013/09/04 06:00 PHST- 2012/12/02 00:00 [received] PHST- 2013/05/21 00:00 [accepted] PHST- 2013/09/04 06:00 [entrez] PHST- 2013/09/04 06:00 [pubmed] PHST- 2014/06/17 06:00 [medline] PHST- 2014/05/01 00:00 [pmc-release] AID - pr2013146 [pii] AID - 10.1038/pr.2013.146 [doi] PST - ppublish SO - Pediatr Res. 2013 Nov;74(5):517-24. doi: 10.1038/pr.2013.146. Epub 2013 Sep 2.