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Kidins220/ARMS 在神经母细胞瘤肿瘤中表达，并在人神经母细胞瘤细胞系中稳定神经营养信号。

Kidins220/ARMS is expressed in neuroblastoma tumors and stabilizes neurotrophic signaling in a human neuroblastoma cell line.

机构信息

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.

出版信息

Pediatr Res. 2013 Nov;74(5):517-24. doi: 10.1038/pr.2013.146. Epub 2013 Sep 2.

DOI:10.1038/pr.2013.146
PMID:23999075
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3968798/
Abstract

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.

摘要

背景

神经营养信号是神经元发育存活的重要因素，神经营养受体的表达与神经母细胞瘤的预后相关。220kDa 的蛋白激酶 D 相互作用底物（Kidins220）与神经营养受体结合并稳定它们，但 Kidins220 在神经母细胞瘤中的表达和功能尚不清楚。

方法

我们通过 Western blot 和微阵列分析研究了 Kidins220 在人神经母细胞瘤细胞系和肿瘤样本中的表达。我们使用小干扰 RNA 沉默和测量细胞存活、信号转导和迁移来确定下调 Kidins220 对细胞系对氧化应激、化疗和神经营养因子反应的功能后果。

结果

Kidins220 在所有研究的神经母细胞瘤肿瘤和细胞系中均有表达。下调 Kidins220 导致神经生长因子（NGF）诱导的但不是脑源性神经营养因子（BDNF）诱导的 MAPK 信号转导减弱。然而，下调 Kidins220 并不改变对化疗药物或氧化应激的反应，也不影响细胞迁移。

结论

Kidins220 在神经母细胞瘤肿瘤中表达，并稳定神经母细胞瘤细胞系中 NGF 诱导的但不是 BDNF 诱导的存活信号。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcc1/3968798/ada0ac071540/nihms-548702-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcc1/3968798/ba9fe9d1340b/nihms-548702-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcc1/3968798/d48a8e8cc502/nihms-548702-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcc1/3968798/eb8937c988bc/nihms-548702-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcc1/3968798/d8aa2cfed861/nihms-548702-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcc1/3968798/ada0ac071540/nihms-548702-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcc1/3968798/ba9fe9d1340b/nihms-548702-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcc1/3968798/d48a8e8cc502/nihms-548702-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcc1/3968798/eb8937c988bc/nihms-548702-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcc1/3968798/d8aa2cfed861/nihms-548702-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcc1/3968798/ada0ac071540/nihms-548702-f0005.jpg

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