Constitutive activation of STAT3 is associated with the acquisition of an interleukin 6-independent phenotype by murine plasmacytomas and hybridomas.

摘要: Interleukin 6 (IL-6), the major growth factor for myeloma cells, signals through activation of signal transducers and activators transcription (STAT) proteins. An important step in malignant progression murine plasmacytomas is transition from dependence on IL-6 to a state independence. To elucidate mechanism whereby independence occurs, intracellular signaling events elicited by both IL-6–dependent –independent hybridomas were compared. It was found that STAT3, key molecule involved signaling, constitutively activated phosphorylated IL-6–independent cell lines compared cells. Further comparison upstream pathways revealed JAK-1 present anti-phosphotyrosine immunoprecipitates cells; gp130 subset plasmacytomas, whereas other showed no detectable phosphorylation absence exogenous IL-6. Secretion capable supporting cells observed one but not others, making an autocrine unlikely explanation These findings provide evidence constitutive either receptor-proximal or associated with concomitant gp130, can contribute process