Interaction of abl and raf with IL-7 signaling pathway and transformation of pre-B cells from resistant mice.
After in vivo inoculation with abl/myc- and raf/myc-containing retroviruses, BALB/c mice predominantly develop late stage B cell tumors (plasmacytomas) and less frequently develop earlier B-lineage tumors while DBA/2 mice do not develop B-lineage tumors. We have investigated the in vitro tumorigenic potential of these viruses using cultured normal pre-B cell lymphocytes from both BALB/c and DBA/2 mice. Interestingly, both viruses infect cultured pre-B lymphocytes from both mouse strains. Following infection, IL-7 dependent pre-B cells become independent of normal in vitro growth requirements within 24 h and can rapidly form in vivo pre-B lymphomas in both mouse strains. Mechanisms mediating loss of IL-7 dependence are different depending on whether the raf or abl gene is present in myc-containing viruses. IL-7 JAK-STAT signaling is constitutively active in abl/myc induced pre-B cell tumors. In contrast, IL-7 JAK-STAT signaling is not constitutive in raf/myc induced pre-B cell tumors, demonstrating that subversion of this component of IL-7 signal transduction is not obligatory for pre-B cell transformation or loss of IL-7 dependence.
Hilbert
D M
DM
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Theisen
P W
PW
Rudikoff
E K
EK
Bauer
S R
SR
D000818:Animals; D001402:B-Lymphocytes; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D015870:Gene Expression; D005822:Genetic Vectors; D007113:Immunity, Innate; D015851:Interleukin-7 / Q000378:metabolism* / Q000494:pharmacology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D010641:Phenotype; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D011533:Proviruses / Q000235:genetics; D012190:Retroviridae / Q000502:physiology; D015398:Signal Transduction; D013234:Stem Cells; D016662:Virus Integration
D015851:Interleukin-7; D016271:Proto-Oncogene Proteins c-myc; D016315:Proto-Oncogene Proteins c-abl; D019908:Proto-Oncogene Proteins c-raf