TY - JOUR
T1 - Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells
AU - Catlett-Falcone, Robyn
AU - Landowski, Terry H.
AU - Oshiro, Marc M.
AU - Turkson, James
AU - Levitzki, Alexander
AU - Savino, Rocco
AU - Ciliberto, Gennaro
AU - Moscinski, Lynn
AU - Fernández-Luna, Jose Luis
AU - Nuñez, Gabriel
AU - Dalton, William S.
AU - Jove, Richard
PY - 1999/1
Y1 - 1999/1
N2 - 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-x(L). Blocking IL-6 receptor signaling from Janus kinases to the Stat3 protein inhibits Bcl-x(L) 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.
AB - 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-x(L). Blocking IL-6 receptor signaling from Janus kinases to the Stat3 protein inhibits Bcl-x(L) 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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U2 - 10.1016/S1074-7613(00)80011-4
DO - 10.1016/S1074-7613(00)80011-4
M3 - Article
C2 - 10023775
AN - SCOPUS:0032984589
VL - 10
SP - 105
EP - 115
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 1
ER -