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

1351 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Apoptosis
Multiple Myeloma
Interleukin-6
Janus Kinases
Interleukin-6 Receptors
Proteins
Survival
Bone Marrow Cells
Neoplasms
Cell Line

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Catlett-Falcone, R., Landowski, T. H., Oshiro, M. M., Turkson, J., Levitzki, A., Savino, R., ... 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

Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. / Catlett-Falcone, Robyn; Landowski, Terry H; Oshiro, Marc M.; Turkson, James; Levitzki, Alexander; Savino, Rocco; Ciliberto, Gennaro; Moscinski, Lynn; Fernández-Luna, Jose Luis; Nuñez, Gabriel; Dalton, William S.; Jove, Richard.

In: Immunity, Vol. 10, No. 1, 01.1999, p. 105-115.

Research output: Contribution to journalArticle

Catlett-Falcone, R, Landowski, TH, Oshiro, MM, Turkson, J, Levitzki, A, Savino, R, Ciliberto, G, Moscinski, L, Fernández-Luna, JL, Nuñez, G, Dalton, WS & Jove, R 1999, 'Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells', Immunity, vol. 10, no. 1, pp. 105-115. https://doi.org/10.1016/S1074-7613(00)80011-4
Catlett-Falcone, Robyn ; Landowski, Terry H ; Oshiro, Marc M. ; Turkson, James ; Levitzki, Alexander ; Savino, Rocco ; Ciliberto, Gennaro ; Moscinski, Lynn ; Fernández-Luna, Jose Luis ; Nuñez, Gabriel ; Dalton, William S. ; Jove, Richard. / Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. In: Immunity. 1999 ; Vol. 10, No. 1. pp. 105-115.
@article{8df01bf8b1924dff94583a4c2b2e4645,
title = "Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells",
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.",
author = "Robyn Catlett-Falcone and Landowski, {Terry H} and Oshiro, {Marc M.} and James Turkson and Alexander Levitzki and Rocco Savino and Gennaro Ciliberto and Lynn Moscinski and Fern{\'a}ndez-Luna, {Jose Luis} and Gabriel Nu{\~n}ez and Dalton, {William S.} and Richard Jove",
year = "1999",
month = "1",
doi = "10.1016/S1074-7613(00)80011-4",
language = "English (US)",
volume = "10",
pages = "105--115",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "1",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=0032984589&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032984589&partnerID=8YFLogxK

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 -