PHOX2A and PHOX2B are differentially regulated during retinoic acid-driven differentiation of SK-N-BE(2)C neuroblastoma cell line

Simona Di Lascio, Elena Saba, Debora Belperio, Andrea Raimondi, Helen Lucchetti, Diego Fornasari, Roberta Benfante

Research output: Contribution to journalArticle

Abstract

PHOX2B and its paralogue gene PHOX2A are two homeodomain proteins in the network regulating the development of autonomic ganglia that have been associated with the pathogenesis of neuroblastoma (NB), because of their over-expression in different NB cell lines and tumour samples. We used the SK-N-BE(2)C cell line to show that all-trans retinoic acid (ATRA), a drug that is widely used to inhibit growth and induce differentiation in NBs, regulates both PHOX2A and PHOX2B expression, albeit by means of different mechanisms: it up-regulates PHOX2A and down-regulates PHOX2B. Both mechanisms act at transcriptional level, but prolonged ATRA treatment selectively degrades the PHOX2A protein, whereas the corresponding mRNA remains up-regulated. Further, we show that PHOX2A is capable of modulating PHOX2B expression, but this mechanism is not involved in the PHOX2B down-regulation induced by retinoic acid. Our findings demonstrate that PHOX2A expression is finely controlled during retinoic acid differentiation and this, together with PHOX2B down-regulation, reinforces the idea that they may be useful biomarkers for NB staging, prognosis and treatment decision making.
Original languageEnglish
Pages (from-to)62 - 71
Number of pages10
JournalExperimental Cell Research
Volume342
Issue number1
DOIs
Publication statusPublished - Mar 1 2016

Keywords

  • Differentiation
  • Homeodomain protein
  • Human
  • Neuroblastoma
  • Retinoic acid
  • Transcription
  • Transcription factor

ASJC Scopus subject areas

  • Cell Biology

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