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PIK3CB/p110β is aselective survivalfactor forglioblastoma Kevin J. PridhamLamvy LeSujuan Guo2017 год

PIK3CB/p110β is a selective survival factor for glioblastoma
статья из журнала

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Аннотация: Glioblastoma (GBM) is difficult to treat. Phosphoinositide 3-kinase (PI3K) is an attractive therapeutic target for GBM; however, targeting this pathway to effectively treat GBM is not successful because the roles of PI3K isoforms remain to be defined. The aim of this study is to determine whether PIK3CB/p110β, but not other PI3K isoforms, is a biomarker for GBM recurrence and important for cell survival.Gene expression and clinical relevance of PI3K genes in GBM patients were analyzed using online databases. Expression/activity of PI3K isoforms was determined using immunoblotting. PI3K genes were inhibited using short hairpin RNAs or isoform-selective inhibitors. Cell viability/growth was assessed by the MTS assay and trypan blue exclusion assay. Apoptosis was monitored using the caspase activity assay. Mouse GBM xenograft models were used to gauge drug efficacy.PIK3CB/p110β was the only PI3K catalytic isoform that significantly correlated with high incidence rate, risk, and poor survival of recurrent GBM. PIK3CA/p110α, PIK3CB/p110β, and PIK3CD/p110δ were differentially expressed in GBM cell lines and primary tumor cells derived from patient specimens, whereas PIK3CG/p110γ was barely detected. PIK3CB/p110β protein levels presented a stronger association with the activities of PI3K signaling than other PI3K isoforms. Blocking p110β deactivated PI3K signaling, whereas inhibition of other PI3K isoforms had no effect. Specific inhibitors of PIK3CB/p110β, but not other PI3K isoforms, remarkably suppressed viability and growth of GBM cells and xenograft tumors in mice, with minimal cytotoxic effects on astrocytes.PIK3CB/p110β is a biomarker for GBM recurrence and selectively important for GBM cell survival.
Год издания: 2017
Авторы: Kevin J. Pridham, Lamvy Le, Sujuan Guo, Robin Varghese, Sarah Algino, Yanping Liang, Renee Fajardin, Cara M. Rodgers, Gary R. Simonds, Deborah F. Kelly, Zhi Sheng
Издательство: Oxford University Press
Источник: Neuro-Oncology
Ключевые слова: Glioma Diagnosis and Treatment, Cancer, Hypoxia, and Metabolism, Neuroblastoma Research and Treatments
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Europe PMC (PubMed Central) (PDF)
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PubMed Central (HTML)
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