Glycogen Synthase Kinase 3 Protein Kinase Activity Is Frequently Elevated in Human Non-Small Cell Lung Carcinoma and Supports Tumour Cell Proliferation

摘要: Background Glycogen synthase kinase 3 (GSK3) is a central regulator of cellular metabolism, development and growth. GSK3 activity was thought to oppose tumourigenesis, yet recent studies indicate that it may support tumour growth in some cancer types including non-small cell lung carcinoma (NSCLC). We examined the undefined role protein tissue from human NSCLC. Methods The expression determined 29 fresh frozen samples NSCLC patient-matched normal by quantitative immunoassay western blotting for phosphorylation three distinct substrates situ (glycogen synthase, RelA CRMP-2). The proliferation sensitivity small-molecule inhibitor; CHIR99021, lines (Hcc193, H1975, PC9 A549) non-neoplastic type II pneumocytes further assessed adherent culture. Results Expression elevated 41% when compared control tissue. Phosphorylation GSK3α/β at inhibitory S21/9 residue poor biomarker samples. inhibitor, CHIR99021 dose-dependently reduced ineffective against pneumocytes. Conclusion NSCLC tumours with have evolved dependence on sustained Our results provide important rationale exploring use inhibitors treating NSCLC.