Activation of the phosphatidylinositol 3'-kinase/AKT pathway in neuroblastoma and its regulation by thioredoxin 1.

摘要: Neuroblastoma is a malignant pediatric tumor with poor survival. The phosphatidylinositol 3'-kinase/AKT pathway crucial regulator of cellular processes including apoptosis. Thioredoxin 1, an inhibitor tumor-suppressor phosphatase and tensin homolog, overexpressed in many tumors. objective this study was to explore activation regulation by thioredoxin 1 identify potential therapeutic targets. Immunohistochemical analysis done on tissue microarrays from samples 101 patients, using antibodies against 3'-kinase, AKT, activated phosphorylated epidermal growth factor receptor, vascular endothelial receptors (vascular receptor 2), platelet-derived receptors, insulin-like neurotrophic tyrosine kinase type 2, 70-kd S6 protein kinase, 4E-binding mammalian target rapamycin. Using 3 neuroblastoma cell lines, we investigated viability AKT-specific inhibitors (LY294002, RAD001) alone or combination. We found AKT expressed 97% 98%, respectively, neuroblastomas, despite high expression homolog correlated 1. greater metastatic than primary Insulin-like downstream were AKT. LY294002 RAD001 significantly reduced activity induced G(1) cycle arrest. decreased cytotoxicity doxorubicin, up-regulated activation, growth. Thus, emerged as preferentially committed observed neuroblastoma. for intervention.