Intracellular distribution of β-catenin in human medulloblastoma cell lines with different degree of neuronal differentiation

Roberta Salaroli, Alessandra Russo, Claudio Ceccarelli, Giorgia D. Mina, Antonella Arcella, Giuseppe N. Martinelli, Felice Giangaspero, Giovanni Capranico, Giovanna Cenacchi

Research output: Contribution to journalArticle

Abstract

Gene mutations impairing the functions of the WNT signaling transduction pathway have been found in approximately 15% of human sporadic medulloblastomas. To understand the functional role of the WNT pathway in medulloblastoma, we have investigated the intracellular distribution of β-catenin in a series of 17 human medulloblastomas to correlate such expression with neuronal differentiation and in cultured cell models following functional silencing of the APC gene by small-interference RNA (siRNA). Transient siRNA transfection resulted in a 50% reduction of the APC gene product levels in both DAOY and D283MED cell lines. In the former, less-differentiated cell line, β-catenin levels remained unchanged or were slightly reduced, but β-catenin translocated in the nucleus following APC gene siRNA silencing. In contrast, in the more differentiated D283MED cells, β-catenin levels increased about twofold while mainly maintaining the cytoplasmic and cell membrane localization. Cytoplasmic/nuclear localization of β-catenin was present in 12 of 17 cases of medulloblastoma with a prevalent distribution in the classic, 6/7 cases, and large cell/anaplastic variant, 4/4 cases. The nodular/desmoplastic lesions showed strongly positivity in the cell membrane mainly of intranodular cells with advanced neuronal differentiation. These observations support an important functional role of WNT/β-catenin pathway in neuronal differentiation in medulloblastoma.

Original languageEnglish
Pages (from-to)33-44
Number of pages12
JournalUltrastructural Pathology
Volume31
Issue number1
DOIs
Publication statusPublished - Feb 2007

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Keywords

  • β-catenin
  • Adenomatous polyposis coli (APC)
  • Electron microscopy
  • Medulloblastoma
  • Small-interfering RNAs (siRNA)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Instrumentation
  • Structural Biology

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