Neuralized1 causes apoptosis and downregulates Notch target genes in medulloblastoma

Natalia Teider, Deborah K. Scott, Adrianne Neiss, S. Dilhan Weeraratne, Vladimir M. Amani, Yifei Wang, Victor E. Marquez, Yoon-Jae Cho, Scott L. Pomeroy

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Neuralized (Neurl) is a highly conserved E3 ubiquitin ligase, which in Drosophila acts upon Notch ligands to regulate Notch pathway signaling. Human Neuralized1 (NEURL1) was investigated as a potential tumor suppressor in medulloblastoma (MB). The gene is located at 10q25.1, a region demonstrating frequent loss of heterozygosity in tumors. In addition, prior publications have shown that the Notch pathway is functional in a proportion of MB tumors and that Neurl1 is only expressed in differentiated cells in the developing cerebellum. In this study, NEURL1 expression was downregulated in MB compared with normal cerebellar tissue, with the lowest levels of expression in hedgehogactivated tumors. Control of gene expression by histone modification was implicated mechanistically; loss of 10q, sequence mutation, and promoter hypermethylation did not play major roles. NEURL1-transfected MB cell lines demonstrated decreased population growth, colony-forming ability, tumor sphere formation, and xenograft growth compared with controls, and a significant increase in apoptosis was seen on cell cycle and cell death analysis. Notch pathway inhibition occurred on the exogenous expression of NEURL1, as shown by decreased expression of the Notch ligand, Jagged1, and the target genes, HES1 and HEY1. From these studies, we conclude that NEURL1 is a candidate tumor suppressor in MB, at least in part through its effects on the Notch pathway.

Original languageEnglish (US)
Pages (from-to)1244-1256
Number of pages13
JournalNeuro-Oncology
Volume12
Issue number12
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

Fingerprint

Medulloblastoma
Down-Regulation
Apoptosis
Genes
Neoplasms
Histone Code
Ligands
Ubiquitin-Protein Ligases
Loss of Heterozygosity
Population Growth
Heterografts
Cerebellum
Drosophila
Publications
Cell Cycle
Cell Death
Gene Expression
Cell Line
Mutation
Growth

Keywords

  • Deazaneplanocin
  • Jagged1
  • Neuralized1
  • Notch
  • Tumor suppressor

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Teider, N., Scott, D. K., Neiss, A., Weeraratne, S. D., Amani, V. M., Wang, Y., ... Pomeroy, S. L. (2010). Neuralized1 causes apoptosis and downregulates Notch target genes in medulloblastoma. Neuro-Oncology, 12(12), 1244-1256. https://doi.org/10.1093/neuonc/noq091

Neuralized1 causes apoptosis and downregulates Notch target genes in medulloblastoma. / Teider, Natalia; Scott, Deborah K.; Neiss, Adrianne; Weeraratne, S. Dilhan; Amani, Vladimir M.; Wang, Yifei; Marquez, Victor E.; Cho, Yoon-Jae; Pomeroy, Scott L.

In: Neuro-Oncology, Vol. 12, No. 12, 01.12.2010, p. 1244-1256.

Research output: Contribution to journalArticle

Teider, N, Scott, DK, Neiss, A, Weeraratne, SD, Amani, VM, Wang, Y, Marquez, VE, Cho, Y-J & Pomeroy, SL 2010, 'Neuralized1 causes apoptosis and downregulates Notch target genes in medulloblastoma', Neuro-Oncology, vol. 12, no. 12, pp. 1244-1256. https://doi.org/10.1093/neuonc/noq091
Teider N, Scott DK, Neiss A, Weeraratne SD, Amani VM, Wang Y et al. Neuralized1 causes apoptosis and downregulates Notch target genes in medulloblastoma. Neuro-Oncology. 2010 Dec 1;12(12):1244-1256. https://doi.org/10.1093/neuonc/noq091
Teider, Natalia ; Scott, Deborah K. ; Neiss, Adrianne ; Weeraratne, S. Dilhan ; Amani, Vladimir M. ; Wang, Yifei ; Marquez, Victor E. ; Cho, Yoon-Jae ; Pomeroy, Scott L. / Neuralized1 causes apoptosis and downregulates Notch target genes in medulloblastoma. In: Neuro-Oncology. 2010 ; Vol. 12, No. 12. pp. 1244-1256.
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