Activation of the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway by Retinoic Acid Is Required for Neural Differentiation of SH-SY5Y Human Neuroblastoma Cells

FHL2 interacts with and acts as a functional repressor of Id2 in human neuroblastoma cells

“…However, treatment with RA (1 mM) induced a progressive and remarkable elevation of both FHL2 mRNA and protein levels. In accordance with previous reports (16,37), RA administration led to a marked inhibition of Id2 gene expression. In RA-untreated SH-SY5Y cells, the endogenous interaction of FHL2 and Id2 could not be detected by CoIP assays but could be detected in SH-SY5Y cells with 6 h RA treatment ( Figure 5B).…”

The role of the nuclear Akt activation and Akt inhibitors in all-trans-retinoic acid-differentiated HL-60 cells

“…29 In various cell culture systems, PI3K-Akt signaling has been implicated as a critical pathway for the differentiation of chondrocytes, osteoblasts, and osteoclasts. 30,31 Activation of the PI3K/Akt pathway by retinoic acid is required for neural differentiation of neuroblastoma cells, 32 and Akt2 localizes to the nucleus of the differentiated myoblasts and plays a specific role in the commitment of myoblasts to differentiation. 33 The level and the activity of PI3K, the major upstream regulator of Akt, has been found to progressively increase in the nuclei of ATRA-treated HL-60 cells, 14,15 and the presence of wortmannin, a PI3K inhibitor, prevented ATRAmediated antiproliferative and differentiative effects.…”

Bcl-2 is a key regulator for the retinoic acid-induced apoptotic cell death in neuroblastoma

“…Recent works offer insights into the molecular mechanisms by which ATRA exerts its biological effects on neuroblastomas. All-trans-retinoic acid activates phosphatidylinositol 3 0 -kinase-Akt pathway that plays an important role in neuronal differentiation (Encinas et al, 1999;Lopez-Carballo et al, 2002), and it reduces the expression levels of MYCN (Thiele et al, 1985) and upregulates the cyclin-dependent kinase (CDK) inhibitor p27 KIP1 in association with the ATRA-induced cell cycle arrest in neuroblastoma cells (Lee et al, 1996;Nakamura et al, 2003). In addition, certain neuroblastoma cells underwent apoptosis in response to ATRA (Piacentini et al, 1992;Takada et al, 2001;Nagai et al, 2004).…”