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      Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells.

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          Abstract

          Interleukin 6 (IL-6) is the major survival factor for myeloma tumor cells and induces signaling through the STAT proteins. We report that one STAT family member, Stat3, is constitutively activated in bone marrow mononuclear cells from patients with multiple myeloma and in the IL-6-dependent human myeloma cell line U266. Moreover, U266 cells are inherently resistant to Fas-mediated apoptosis and express high levels of the antiapoptotic protein Bcl-xL. Blocking IL-6 receptor signaling from Janus kinases to the Stat3 protein inhibits Bcl-xL expression and induces apoptosis, demonstrating that Stat3 signaling is essential for the survival of myeloma tumor cells. These findings provide evidence that constitutively activated Stat3 signaling contributes to the pathogenesis of multiple myeloma by preventing apoptosis.

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          Author and article information

          Journal
          Immunity
          Immunity
          Elsevier BV
          1074-7613
          1074-7613
          Jan 1999
          : 10
          : 1
          Affiliations
          [1 ] H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa 33612, USA.
          Article
          S1074-7613(00)80011-4
          10.1016/s1074-7613(00)80011-4
          10023775
          fb406230-acfe-4ece-bb74-99cc4cffe2a1
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