Document Detail

PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation.
MedLine Citation:
PMID:  22766505     Owner:  NLM     Status:  MEDLINE    
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 p27(Kip), 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.
Jingbo Qiao; Pritha Paul; Sora Lee; Lan Qiao; Erlena Josifi; Joshua R Tiao; Dai H Chung
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-07-02
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  424     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-06     Completed Date:  2012-11-19     Revised Date:  2013-08-13    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  421-6     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
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MeSH Terms
Cell Differentiation
Extracellular Signal-Regulated MAP Kinases / metabolism*
G0 Phase
G1 Phase Cell Cycle Checkpoints
Neuroblastoma / enzymology*,  pathology
Phosphatidylinositol 3-Kinases / metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
Tretinoin / pharmacology*
Grant Support
Reg. No./Substance:
302-79-4/Tretinoin; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC Proteins c-akt; EC Signal-Regulated MAP Kinases

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