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

Experimental Cell Research
Simona Di LascioRoberta Benfante

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.

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Citations

Feb 17, 2017·Wiley Interdisciplinary Reviews. Developmental Biology·Stephen R ShannonPaul A Trainor
Aug 25, 2019·Clinical Genetics·Tiziana Bachetti, Isabella Ceccherini
Jan 30, 2021·Frontiers in Neuroscience·Simona Di LascioDiego Fornasari

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Methods Mentioned

BETA
xenograft
PCR
immunoprecipitation
transfection
Assay
transfections

Software Mentioned

MatInspector
GraphPad Prism
NIH Image
SDS

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