Activation of anaplastic lymphoma kinase is responsible for hyperphosphorylation of ShcC in neuroblastoma cell lines

Miyake, Izumi; Hakomori, Yuko; Shinohara, Azusa; Gamou, Toshie; Saito, Masaki; Iwamatsu, Akihiro; Sakai, Ryuichi

doi:10.1038/sj.onc.1205735

Cited by 100 publications

(124 citation statements)

References 48 publications

(54 reference statements)

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“…17 Recent data revealed that in every cohort at least one of 10 MNA samples displayed coamplification of the ALK gene. 5,14,56 Moreover, ALK amplification was identified in samples derived from patients with poor prognosis, 17,55 which is in line with our data (Table 1).…”

Section: Discussionsupporting

confidence: 81%

“…54 Other groups demonstrated that amplification of the ALK gene leads to overexpression of the ALK protein and to constitutively activated ALK kinase. 17,55 The suppression of activated ALK in NB-39-nu ALK amplified cells by RNA interference significantly reduced the phosphorylation of ShcC, mitogen-activated protein kinases, and Akt, inducing rapid apoptosis of the cells. 17 Recent data revealed that in every cohort at least one of 10 MNA samples displayed coamplification of the ALK gene.…”

Section: Discussionmentioning

confidence: 99%

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Genes Proximal and Distal to MYCN Are Highly Expressed in Human Neuroblastoma as Visualized by Comparative Expressed Sequence Hybridization

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Bozsaky

Watzinger

et al. 2008

The American Journal of Pathology

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MYCN amplification is associated with poor prognosis in neuroblastoma disease. To improve our understanding of the influence of the MYCN amplicon and its corresponding expression, we investigated the 2p expression pattern of MYCN amplified (n ‫؍‬ 13) and nonamplified (n ‫؍‬ 4) cell lines and corresponding primary tumors (n ‫؍‬ 3) using the comparative expressed sequence hybridization technique. All but one MYCN amplified cell line displayed overexpression at 2p. Expression peaks were observed frequently at 2pter and less frequently at 2p24 (MYCN locus), 2p23.3-23.2, and/or 2p23.1. Importantly, cell lines and two corresponding primary tumors displayed expression peaks at similar loci. No significant 2p24 expression level was observed for those cell lines displaying a low amplification rate (n ‫؍‬ 3) by comparative genomic hybridization. Only the cell lines with an enhanced peak at 2p23.2-23.3 displayed coamplification of the ALK gene (2p23.2), reported to be associated with unfavorable prognosis. Finally, two of four cell lines without MYCN amplification, both derived from patients with poor outcome, also showed an expression peak at 2p23.2. These data indicate that, besides MYCN, other genes proximal and distal to MYCN are highly expressed in neuroblastoma. The prognostic significance of expression peaks at 2p23.2-23.3, independent of MYCN and ALK status, remains to be investigated.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Genes Proximal and Distal to MYCN Are Highly Expressed in Human Neuroblastoma as Visualized by Comparative Expressed Sequence Hybridization

Stock

Bozsaky

Watzinger

et al. 2008

The American Journal of Pathology

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“…27 The polyclonal antibodies against the CH1 domains of ShcC (amino acids 306 -371) and the anti-ALK antibody (␣ALK) that was against the cytoplasmic portion (amino acid 1379 -1524) of human ALK were prepared as described previously. 27,28 An anti-phosphotyrosine antibody (4G10) was obtained from UBI. Anti-p44/42 MAPKs, anti-phospho-p44/42 MAPKs, anti-Akt, and anti-phospho-Akt antibodies were purchased from Cell Signaling (Beverly, MA).…”

Section: Immunochemical Analysis Of Proteinsmentioning

confidence: 99%

“…In vitro kinase assay for ALK was performed as previously described. 27 Anti-ALK immunoprecipitates were incubated with or without Poly-Glu/Tyr as an exogenous substrate.…”

Section: Immunochemical Analysis Of Proteinsmentioning

confidence: 99%

“…26 We have recently shown using mass-spectrometry analysis that ALK is a major phosphoprotein associated with hyperphosphorylated ShcC in several neuroblastoma cell lines. 27 In these cells, ALK was markedly activated, and it induced the constitutive phosphorylation of ShcC and mitogen-activated protein kinase (MAPK), regardless of stimulation by epidermal growth factor (EGF) or nerve growth factor. 27 These findings strongly suggest that constitutively activated ALK kinase plays a physiological role in the development of neuroblastoma.…”

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confidence: 99%

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Biological Role of Anaplastic Lymphoma Kinase in Neuroblastoma

Osajima-Hakomori¹,

Miyake²,

Ohira³

et al. 2005

The American Journal of Pathology

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Analysis of ALK, MYCN, and the ALK ligand ALKAL2 (FAM150B/AUGα) in neuroblastoma patient samples with chromosome arm 2p rearrangements

Javanmardi

Fransson

Djos

et al. 2019

Genes Chromosomes & Cancer

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Gain of chromosome arm 2p is a previously described entity in neuroblastoma (NB). This genomic address is home to two important oncogenes in NB-MYCN and anaplastic lymphoma kinase (ALK). MYCN amplification is a critical prognostic factor coupled with poor prognosis in NB. Mutation of the ALK receptor tyrosine kinase has been described in both somatic and familial NB. Here, ALK activation occurs in the context of the full-length receptor, exemplified by activating point mutations in NB. ALK overexpression and activation, in the absence of genetic mutation has also been described in NB. In addition, the recently identified ALK ligand ALKAL2 (previously described as FAM150B and AUGα) is also found on the distal portion of 2p, at 2p25. Here we analyze 356 NB tumor samples and discuss observations indicating that gain of 2p has implications for the development of NB. Finally, we put forward the hypothesis that the effect of 2p gain may result from a combination of MYCN, ALK, and the ALK ligand ALKAL2.

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Activation of anaplastic lymphoma kinase is responsible for hyperphosphorylation of ShcC in neuroblastoma cell lines

Cited by 100 publications

References 48 publications

Genes Proximal and Distal to MYCN Are Highly Expressed in Human Neuroblastoma as Visualized by Comparative Expressed Sequence Hybridization

Genes Proximal and Distal to MYCN Are Highly Expressed in Human Neuroblastoma as Visualized by Comparative Expressed Sequence Hybridization

Biological Role of Anaplastic Lymphoma Kinase in Neuroblastoma

Analysis of ALK, MYCN, and the ALK ligand ALKAL2 (FAM150B/AUGα) in neuroblastoma patient samples with chromosome arm 2p rearrangements

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