PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation.
Biochem Biophys Res Commun
; 424(3): 421-6, 2012 Aug 03.
Article
en En
| MEDLINE
| ID: mdl-22766505
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 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tretinoina
/
Fosfatidilinositol 3-Quinasas
/
Quinasas MAP Reguladas por Señal Extracelular
/
Proteínas Proto-Oncogénicas c-akt
/
Neuroblastoma
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos