Distinct tumorigenic potential of abl and raf in B cell neoplasia: abl activates the IL-6 signaling pathway.
The development of murine plasma cell tumors induced by raf/myc containing retroviruses is facilitated by T cells and completely dependent on IL-6. To determine whether kinases with differing specificities reflect alternative biochemical pathways in B cell tumorigenesis, we have employed an abl/myc containing retrovirus to assess neoplastic development. In contrast with raf/myc, abl/myc disease is T cell and IL-6 independent. An examination of the IL-6 signal transduction pathway reveals that this pathway, as defined by activation of Stat3, is inducible by IL-6 in raf/myc tumors but constitutively activated in abl/myc tumors. These findings provide a mechanism for the derivation of cytokine-independent plasma cell tumors and suggest that both IL-6-dependent and independent tumors may arise in vivo depending on the particular mutational events incurred during tumorigenesis.
Hilbert
D M
DM
Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Migone
T S
TS
Kopf
M
M
Leonard
W J
WJ
Rudikoff
S
S
D000818:Animals; D001483:Base Sequence; D016313:Genes, abl / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010641:Phenotype; D010954:Plasmacytoma / Q000235:genetics* / Q000276:immunology; D012192:Retroviridae Infections / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology*; D014412:Tumor Virus Infections / Q000235:genetics* / Q000276:immunology
D015850:Interleukin-6