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Open Access Research article

Aggressive neuroblastomas have high p110alpha but low p110delta and p55alpha/p50alpha protein levels compared to low stage neuroblastomas

Susanne Fransson14*, Per Kogner2, Tommy Martinsson4 and Katarina Ejeskär13

Author Affiliations

1 Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, SE-405 30, Gothenburg, Sweden

2 Department of Women’s and Children’s Health, Childhood Cancer Research Unit, Karolinska Institutet, SE-171 76, Stockholm, Sweden

3 School of Life sciences, University of Skövde, SE-541 28, Skövde, Sweden

4 Department of Medical and Clinical Genetics, University of Gothenburg, Sahlgrenska University Hospital, S-413 45, Gothenburg, Sweden

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Journal of Molecular Signaling 2013, 8:4  doi:10.1186/1750-2187-8-4

Published: 18 April 2013

Abstract

Background

The phosphoinositide 3-kinase (PI3K)/Akt pathway is involved in neuroblastoma development where Akt/PKB activation is associated with poor prognosis. PI3K activity subsequently activates Akt/PKB, and as mutations of PI3K are rare in neuroblastoma and high levels of PI3K subunit p110delta is associated with favorable disease with low p-Akt/PKB, the levels of other PI3K subunits could be important for Akt activation.

Methods

Protein levels of Type IA PI3K catalytic and regulatory subunits were investigated together with levels of phosphorylated Akt/PKB and the PI3K negative regulator PTEN in primary neuroblastoma tumors. Relation between clinical markers and protein levels were evaluated through t-tests.

Results

We found high levels of p-Akt/PKB correlating to aggressive disease and p-Akt/PKB (T308) showed inverse correlation to PTEN levels. The regulatory isomers p55alpha/p50alpha showed higher levels in favorable neuroblastoma as compared with aggressive neuroblastoma. The PI3K-subunit p110alpha was found mainly in advanced tumors while p110delta showed higher levels in favorable neuroblastoma.

Conclusions

Activation of the PI3K/Akt pathway is seen in neuroblastoma tumors, however the contribution of the different PI3K isoforms is unknown. Here we show that p110alpha is preferentially expressed in aggressive neuroblastomas, with high p-Akt/PKB and p110delta is mainly detected in favorable neuroblastomas, with low p-Akt/PKB. This is an important finding as PI3K-specific inhibitors are suggested for enrollment in treatment of neuroblastoma patients.

Keywords:
Neuroblastoma; PI3K; Akt; Signaling; Phosphoinositide 3-kinase