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

Journal of Molecular Signaling

Katarina Ejeskär¹  Tommy Martinsson³  Per Kogner²  Susanne Fransson³ 

[1] School of Life sciences, University of Skövde, SE-541 28, Skövde, Sweden;Department of Women’s and Children’s Health, Childhood Cancer Research Unit, Karolinska Institutet, SE-171 76, Stockholm, Sweden;Department of Medical and Clinical Genetics, University of Gothenburg, Sahlgrenska University Hospital, S-413 45, Gothenburg, Sweden

关键词: Phosphoinositide 3-kinase;    Signaling;    Akt;    PI3K;    Neuroblastoma;   

Others  :  802642
DOI  :  10.1186/1750-2187-8-4

 received in 2012-10-05, accepted in 2013-04-05,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Fransson et al.; licensee BioMed Central Ltd.

【 图 表 】

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