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

Robyn Catlett-Falcone, Terry H. Landowski, Marc M. Oshiro, James Turkson, Alexander Levitzki, Rocco Savino, Gennaro Ciliberto, Lynn Moscinski, Jose Luis Fernández-Luna, Gabriel Nuñez, William S. Dalton, Richard Jove

Research output: Contribution to journalArticle

1368 Scopus citations

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-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.

Original languageEnglish (US)
Pages (from-to)105-115
Number of pages11
JournalImmunity
Volume10
Issue number1
DOIs
StatePublished - Jan 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Catlett-Falcone, R., Landowski, T. H., Oshiro, M. M., Turkson, J., Levitzki, A., Savino, R., Ciliberto, G., Moscinski, L., Fernández-Luna, J. L., Nuñez, G., Dalton, W. S., & Jove, R. (1999). Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity, 10(1), 105-115. https://doi.org/10.1016/S1074-7613(00)80011-4