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Clin Cancer Res. 2008 Feb 15;14(4):1172-81. doi: 10.1158/1078-0432.CCR-07-0737.

Targeting the phosphoinositide 3-kinase isoform p110delta impairs growth and survival in neuroblastoma cells.

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  • 1Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, Switzerland.

Abstract

PURPOSE:

The phosphoinositide 3-kinase (PI3K)/Akt pathway is frequently activated in human cancer and plays a crucial role in neuroblastoma biology. 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.

PMID:
18281552
[PubMed - indexed for MEDLINE]
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