We previously demonstrated that PI3K Class IIβ (PI3KC2β) and its regulator intersectin 1 (ITSN1) are highly expressed in primary NB tumors and cell lines.
In this study we investigated the phosphorylation status of key proteins in the PI3K/AKT/mTOR pathway and the effects of the mTOR inhibitors rapamycin and CCI-779 on neuroblastoma tumorigenesis.
Activating mutations of the NRAS (neuroblastoma rat sarcoma viral oncogene) protein kinase, present in many cancers, induce a constitutive activation of both the RAS-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) signal transduction pathway and the PI(3)K-AKT-mTOR, pathway.
Our previous studies have demonstrated that PI3K/AKT signaling is critical for the oncogenic transformations induced by gastrin-releasing peptide (GRP) and its receptor, GRP-R, in neuroblastoma.
Our data also suggest that the phosphoinositide 3-kinase (PI3K) inhibitors may provide new opportunities for the treatment of the <i>MYCN</i>-amplified neuroblastoma subtype.
Palmitic acid stimulates energy metabolism and inhibits insulin/PI3K/AKT signaling in differentiated human neuroblastoma cells: The role of mTOR activation and mitochondrial ROS production.
We hypothesize that VEGF will up-regulate survivin, a member of the IAP family of anti-apoptotic proteins, via the PI3K/Akt cell signaling pathway in human neuroblastoma cells.
However, NVP-BEZ235, a potent dual PI3K and mTOR inhibitor have not shown beneficial effects on neuroblastoma especially in terms of apoptosis induction as a single agent.
Pharmacological inhibition of PI3K greatly reduced the ability of PDGF-BB to block gp120 IIIB-mediated apoptosis and cell death in human neuroblastoma cells.
Both MAPK and PI3K pathways were involved in BDNF protection of NB cells from paclitaxel-induced cell death, while PI3K predominantly mediated BDNF protection of NB cells from etoposide or cisplatin-induced cell death.
This decline in mTOR activity was accompanied by an increase in phosphoinositide 3 kinase (PI3K)/Akt activity and a parallel increase in p-tau (Ser<sup>396</sup>) but not p-tau (Ser<sup>262</sup>) in differentiated SH-SY5Y neuroblastoma cells.
The PI3K inhibitor PI103 cooperates with TRAIL to synergistically induce apoptosis (combination index < 0.1), to suppress clonogenic survival, and to reduce tumor growth in a neuroblastoma in vivo model.
SF1126 inhibits BRD4 bromodomain binding to acetylated lysine residues with histone H3 as well as PI3K activity in the MYCN amplified neuroblastoma cell line IMR-32.
We show that the glial cell line-derived neurotrophic factor (GDNF) activates the PI3K/Akt-signaling pathway in human neuroblastoma cells that express functional Ret-receptor complexes.