PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation

Jingbo Qiao, Pritha Paul, Sora Lee, Lan Qiao, Erlena Josifi, Joshua R. Tiao, Dai H. Chung

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Neuroblastoma, the most common extra-cranial solid tumor in infants and children, is characterized by a high rate of spontaneous remissions in infancy. Retinoic acid (RA) has been known to induce neuroblastoma differentiation; however, the molecular mechanisms and signaling pathways that are responsible for RA-mediated neuroblastoma cell differentiation remain unclear. Here, we sought to determine the cell signaling processes involved in RA-induced cellular differentiation. Upon RA administration, human neuroblastoma cell lines, SK-N-SH and BE(2)-C, demonstrated neurite extensions, which is an indicator of neuronal cell differentiation. Moreover, cell cycle arrest occurred in G1/G0 phase. The protein levels of cyclin-dependent kinase inhibitors, p21 and p27Kip, which inhibit cell proliferation by blocking cell cycle progression at G1/S phase, increased after RA treatment. Interestingly, RA promoted cell survival during the differentiation process, hence suggesting a potential mechanism for neuroblastoma resistance to RA therapy. Importantly, we found that the PI3K/AKT pathway is required for RA-induced neuroblastoma cell differentiation. Our results elucidated the molecular mechanism of RA-induced neuroblastoma cellular differentiation, which may be important for developing novel therapeutic strategy against poorly differentiated neuroblastoma.

Original languageEnglish (US)
Pages (from-to)421-426
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume424
Issue number3
DOIs
StatePublished - Aug 3 2012
Externally publishedYes

Keywords

  • Differentiation
  • ERK
  • Neuroblastoma
  • PI3K
  • Retinoic acid

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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