Targeting the Phosphoinositide 3-Kinase Isoform p110delta Impairs Growth and Survival in Neuroblastoma Cells

Boller D, Schramm A, Doepfner KT, Shalaby T, von Bueren AO, Eggert A, Grotzer MA, Arcaro A
Source: Clin Cancer Res
Publication Date: (2008)
Issue: 14(4): 1172-1181
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
Species: human
Tissue Origin: brain
Nucleofectorâ„¢ I/II/2b
We were interested in gaining further insight into the potential of targeting PI3K/Akt signaling as a novel antiproliferative approach in neuroblastoma. EXPERIMENTAL DESIGN: The expression pattern and functions of class I(A) PI3K isoforms were investigated in tumor samples and cell lines. Effects on cell survival and downstream signaling were analyzed following down-regulation of p110alpha or p110delta in SH-SY5Y and LA-N-1 cells by means of RNA interference. RESULTS: Overexpression of the catalytic p110delta and regulatory p85alpha isoforms was detected in a panel of primary neuroblastoma samples and cell lines, compared with normal adrenal gland tissue. Although down-regulation of either p110alpha or p110delta led to impaired cell growth, reduced expression of p110delta also had a selective effect on the survival of SH-SY5Y cells. Decreased levels of p110delta were found to induce apoptosis and lead to lower expression levels of antiapoptotic Bcl-2 family proteins. SH-SY5Y cells with decreased p110delta levels also displayed reduced activation of ribosomal protein S6 kinase in response to stimulation with epidermal growth factor and insulin-like growth factor-I. CONCLUSIONS: Together, our data reveal a novel function of p110delta in neuroblastoma growth and survival.