The neural progenitor-restricted isoform of the MARK4 gene in 19q13.2 is upregulated in human gliomas and overexpressed in a subset of glioblastoma cell lines

Alessandro Beghini, Ivana Magnani, Gaia Roversi, Tiziana Piepoli, Simona Di Terlizzi, Ramona F. Moroni, Bianca Pollo, Anna M. Fuhrman Conti, John K. Cowell, Gaetano Finocchiaro, Lidia Larizza

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Alterations of 19q13 are frequently observed in glial neoplasms, suggesting that this region harbors at least one gene involved in gliomagenesis. Following our previous studies on structural 19q chromosome rearrangements in gliomas, we have undertaken a detailed FISH analysis of the breakpoints and identified a 19q13.2 intrachromosoreal amplification of the MAP/microtubule affinity-regulating kinase 4 (MARK4) gene in three primary glioblastoma cell lines. Recent data suggest that this gene is involved in the Wnt-signaling pathway. We observed that the expression of the alternatively spliced MARK4L isoform is upregulated in both fresh and cultured gliomas and overexpressed in all of the above three glioblastoma cell lines. Interestingly, we also found that MARK4L expression is restricted to undifferentiated neural progenitor cells or proliferating glial precursor cells, whereas its expression is downregulated during glial differentiation. Perturbation of expression using antisense oligonucleotides against MARK4 in glioblastoma cell lines, consistently induced a decreased proliferation of tumor cells. Taken together, these data show that MARK4, which is normally expressed in neural progenitors, is reexpressed in gliomas and may become a key target of intrachromosomal amplification upon 19q rearrangements.

Original languageEnglish (US)
Pages (from-to)2581-2591
Number of pages11
JournalOncogene
Volume22
Issue number17
DOIs
StatePublished - May 1 2003
Externally publishedYes

Keywords

  • Glioma
  • Intrachromosomal amplification
  • MARK4
  • Neural progenitor
  • Upregulation and overexpression
  • Wnt pathway

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Beghini, A., Magnani, I., Roversi, G., Piepoli, T., Di Terlizzi, S., Moroni, R. F., Pollo, B., Fuhrman Conti, A. M., Cowell, J. K., Finocchiaro, G., & Larizza, L. (2003). The neural progenitor-restricted isoform of the MARK4 gene in 19q13.2 is upregulated in human gliomas and overexpressed in a subset of glioblastoma cell lines. Oncogene, 22(17), 2581-2591. https://doi.org/10.1038/sj.onc.1206336