Analysis of signal transducer and activator of transcription 3 (STAT3) in gastrointestinal stromal tumors.

摘要: Several signaling pathways have been recognized in normal c-kit-mediated signal transduction following stem cell factor (SCF) stimulation including Janus kinase (JAK)/signal transducer and activator of transcription (STAT), mitogen-activated protein (MAPK) phosphoinositol 3-kinase (PI-3 K) pathways. In gastrointestinal stromal tumor (GIST), c-kit activation is considered to play a central role its tumorigenesis. However, the cascades specific for SCF-independent GIST remains be elucidated. this study, we examined expression activated form STAT3 [phospho-STAT3 (tyr 705)] eleven cases by immunohistochemistry. All GISTs had strong nuclear variable cytoplasmic phospho-STAT3 705). Survival proliferation two established primary lines with exon-11 mutations were then assessed their response inhibitors (STI-571), JAK 2 (Tyrphostin AG490), MAPK (PD98059) PI-3 K(LY294002). cells showed significant inhibition apoptosis when treated STI571 or AG490 but not PD98059 LY294002. Bcl-2 was expressed all (11 out 11) down-regulated treatment AG490. This study demonstrates that constitutively JAK2 blockade leads growth indicating involvement JAK/STAT pathway cellular survival.