Targeting the Phosphoinositide 3-Kinase Isoform p110δ Impairs Growth and Survival in Neuroblastoma Cells
| Autor: | André O. von Bueren, Tarek Shalaby, Danielle Boller, Angelika Eggert, Alexandre Arcaro, Alexander Schramm, Kathrin T. Doepfner, Michael A. Grotzer |
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| Přispěvatelé: | University of Zurich, Arcaro, A |
| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
medicine.medical_specialty Cell Survival Blotting Western Medizin Gene Expression 610 Medicine & health Apoptosis Neuroblastoma Phosphatidylinositol 3-Kinases Epidermal growth factor Cell Line Tumor Internal medicine medicine Humans 1306 Cancer Research Protein kinase B Cells Cultured PI3K/AKT/mTOR pathway Cell Proliferation Phosphoinositide 3-kinase biology Reverse Transcriptase Polymerase Chain Reaction Cell growth Gene Expression Profiling TOR Serine-Threonine Kinases medicine.disease Isoenzymes Endocrinology Proto-Oncogene Proteins c-bcl-2 Oncology 10036 Medical Clinic Cell culture P110δ Cancer research biology.protein 2730 Oncology Protein Kinases |
| Zdroj: | Clinical Cancer Research. 14:1172-1181 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-07-0737 |
| Popis: | 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 IA PI3K isoforms were investigated in tumor samples and cell lines. Effects on cell survival and downstream signaling were analyzed following down-regulation of p110α or p110δ in SH-SY5Y and LA-N-1 cells by means of RNA interference.Results: Overexpression of the catalytic p110δ and regulatory p85α isoforms was detected in a panel of primary neuroblastoma samples and cell lines, compared with normal adrenal gland tissue. Although down-regulation of either p110α or p110δ led to impaired cell growth, reduced expression of p110δ also had a selective effect on the survival of SH-SY5Y cells. Decreased levels of p110δ were found to induce apoptosis and lead to lower expression levels of antiapoptotic Bcl-2 family proteins. SH-SY5Y cells with decreased p110δ 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 p110δ in neuroblastoma growth and survival. |
| Databáze: | OpenAIRE |
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