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

doi:10.1016/S1074-7613(00)80011-4

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

Cancer Center

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1497 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 language	English (US)
Pages (from-to)	105-115
Number of pages	11
Journal	Immunity
Volume	10
Issue number	1
DOIs	https://doi.org/10.1016/S1074-7613(00)80011-4
State	Published - Jan 1999

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

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@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",

note = "Funding Information: We thank Anne Hudnall for performing preliminary studies, Bobbye Hill for providing cells, Daniel Sullivan and Bill Janssen for help with obtaining clinical specimens, Hong-Gang Wang for helpful comments on the manuscript, members of the laboratory for stimulating discussion, and the Molecular Biology, Flow Cytometry, and Molecular Imaging core facilities of Moffitt Cancer Center. This work was supported by NIH grants CA77859 (W. S. D.) and CA55652 (R. J.).",

year = "1999",

month = jan,

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",

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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

N1 - Funding Information: We thank Anne Hudnall for performing preliminary studies, Bobbye Hill for providing cells, Daniel Sullivan and Bill Janssen for help with obtaining clinical specimens, Hong-Gang Wang for helpful comments on the manuscript, members of the laboratory for stimulating discussion, and the Molecular Biology, Flow Cytometry, and Molecular Imaging core facilities of Moffitt Cancer Center. This work was supported by NIH grants CA77859 (W. S. D.) and CA55652 (R. J.).

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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DO - 10.1016/S1074-7613(00)80011-4

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AN - SCOPUS:0032984589

SN - 1074-7613

VL - 10

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JO - Immunity

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ER -

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

Abstract

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