The metallophosphodiesterase Mpped2 impairs tumorigenesis in neuroblastoma

Lucia Liguori, Immacolata Andolfo, Pasqualino De Antonellis, Veruska Aglio, Valeria Di Dato, Natascia Marino, Nicola Ivan Orlotti, Daniela De Martino, Mario Capasso, Giuseppe Petrosino, Alexander Schramm, Luigi Navas, Gian Paolo Tonini, Angelika Eggert, Achille Iolascon, Massimo Zollo

Research output: Contribution to journalArticle

Abstract

Through microarray analyses, we identified the Mpped2 gene as differentially expressed in two neuroblastoma cell lines induced to differentiation with all-trans retinoic acid. Mpped2 codes for a new metallophosphodiesterase protein, the expression of which inhibits cell proliferation and soft agar colony formation in SH -SY5Y cells. This inhibition is concomitant to an increased proportion of the cells in G0/G 1 phase and enhanced caspase 3 activation, effects not seen for the other phosphodiesterases. A Mpped2-null mutation (H67R) abrogates these functions, which indicates that the biochemical activity of Mpped2 is advantageous for cancer suppression. Expression analyses in the "Los Angeles" and "Essen" neuroblastoma gene-array data sets show that increased expression of Mpped2 is associated with good patient prognosis according to Kaplan-Meier analyses. Tumorigenic assays in mice show that overexpression of Mpped2 improves survival rate, substantially impairs tumor growth and induces neuronal differentiation. Altogether, these data show that Mpped2 expression impairs neuroblastoma tumorigenesis, and they establish a basis for future therapeutic applications.

Original languageEnglish
Pages (from-to)569-581
Number of pages13
JournalCell Cycle
Volume11
Issue number3
DOIs
Publication statusPublished - Feb 1 2012

Keywords

  • Gene expression
  • Mpped2
  • Neuroblastoma
  • Retinoic acid
  • Xenograft

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'The metallophosphodiesterase Mpped2 impairs tumorigenesis in neuroblastoma'. Together they form a unique fingerprint.

  • Cite this

    Liguori, L., Andolfo, I., De Antonellis, P., Aglio, V., Di Dato, V., Marino, N., Orlotti, N. I., De Martino, D., Capasso, M., Petrosino, G., Schramm, A., Navas, L., Tonini, G. P., Eggert, A., Iolascon, A., & Zollo, M. (2012). The metallophosphodiesterase Mpped2 impairs tumorigenesis in neuroblastoma. Cell Cycle, 11(3), 569-581. https://doi.org/10.4161/cc.11.3.19063