Meningioma transcript profiles reveal deregulated Notch signaling pathway

Ileana C. Cuevas, Alison L. Slocum, Peter Jun, Joseph F. Costello, Andrew W. Bollen, Gregory J. Riggins, Michael W. McDermott, Anita Lal

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Meningiomas constitute the second most common central nervous system tumor, and yet relatively little is known about the molecular events that are important for the pathogenesis and malignant progression of these tumors. We have used serial analysis of gene expression to compare the transcriptomes of nonneoplastic meninges and meningiomas of all malignancy grades. A novel finding from this screen is the induction of three components of the Notch signaling pathway: the transcription factor, hairy and enhancer of Split1 (HES1) and two members of the Groucho/transducin-like enhancer of Split family of corepressors, TLE2 and TLE3. TLE corepressors interact and modulate the activity of a wide range of transcriptional regulatory systems, one of which is HES1. We have shown that the transcript and protein levels of HES1, the Notch2 and Notch1 receptors and the Jagged1 ligand are induced in meningiomas of all grades, whereas induction of TLE2 and TLE3 occurs specifically in higher-grade meningiomas. Meningioma cell lines express components of the Notch signaling pathway and an inhibitor of this pathway suppresses meningioma cell survival. These results suggest that deregulated expression of the Notch pathway is a critical event in meningioma pathogenesis and that modulation of this and potentially other signaling pathways by TLE corepressors leads to a more malignant phenotype.

Original languageEnglish (US)
Pages (from-to)5070-5075
Number of pages6
JournalCancer Research
Volume65
Issue number12
DOIs
StatePublished - Jun 15 2005

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Meningioma
Co-Repressor Proteins
Notch2 Receptor
Notch1 Receptor
Transducin
Meninges
Central Nervous System Neoplasms
Transcriptome
Neoplasms
Cell Survival
Transcription Factors
Ligands
Phenotype
Gene Expression
Cell Line
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cuevas, I. C., Slocum, A. L., Jun, P., Costello, J. F., Bollen, A. W., Riggins, G. J., ... Lal, A. (2005). Meningioma transcript profiles reveal deregulated Notch signaling pathway. Cancer Research, 65(12), 5070-5075. https://doi.org/10.1158/0008-5472.CAN-05-0240

Meningioma transcript profiles reveal deregulated Notch signaling pathway. / Cuevas, Ileana C.; Slocum, Alison L.; Jun, Peter; Costello, Joseph F.; Bollen, Andrew W.; Riggins, Gregory J.; McDermott, Michael W.; Lal, Anita.

In: Cancer Research, Vol. 65, No. 12, 15.06.2005, p. 5070-5075.

Research output: Contribution to journalArticle

Cuevas, IC, Slocum, AL, Jun, P, Costello, JF, Bollen, AW, Riggins, GJ, McDermott, MW & Lal, A 2005, 'Meningioma transcript profiles reveal deregulated Notch signaling pathway', Cancer Research, vol. 65, no. 12, pp. 5070-5075. https://doi.org/10.1158/0008-5472.CAN-05-0240
Cuevas IC, Slocum AL, Jun P, Costello JF, Bollen AW, Riggins GJ et al. Meningioma transcript profiles reveal deregulated Notch signaling pathway. Cancer Research. 2005 Jun 15;65(12):5070-5075. https://doi.org/10.1158/0008-5472.CAN-05-0240
Cuevas, Ileana C. ; Slocum, Alison L. ; Jun, Peter ; Costello, Joseph F. ; Bollen, Andrew W. ; Riggins, Gregory J. ; McDermott, Michael W. ; Lal, Anita. / Meningioma transcript profiles reveal deregulated Notch signaling pathway. In: Cancer Research. 2005 ; Vol. 65, No. 12. pp. 5070-5075.
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