M. Hamdane et al., ACTIVATION OF P65 NF-KAPPA-B PROTEIN BY P210(BCR-ABL) IN MYELOID CELL-LINE (P210(BCR-ABL) ACTIVATES P65 NF-KAPPA-B), Oncogene, 15(19), 1997, pp. 2267-2275
The chimeric tyrosine kinase p210(BCR-ABL) is involved in the pathogen
esis of chronic myelogenous leukemia. It transforms immature hematopoi
etic cells in vitro and abrogates IL-3-dependent growth. The mechanism
s by which p210(BCR-ABL) mediates its oncogenicity are not well elucid
ated. Identifying transcription factors targeted by the chimeric prote
in may help to clarify these mechanisms. We have analysed the effect o
f p210(BCR-ABL) expression on NF-kappa B activity in DA1 cells (an IL-
3-dependent murine myeloid progenitor cell line). A specific stimulati
on of NF-kappa B activity by kinase-active wild-type p210(BCR-ABL) has
been evidenced by transcriptional activation assays. Electrophoretic
mobility supershift assays revealed the presence of p65 protein (RelA)
DNA binding activity in p210(BCR-ABL) transformed DA1 cells but not i
n parental DA1 cells. Activation of RelA in transformed DA1 cells may
occur by protein stabilization. Experiments using oligonucleotides ant
isense to RelA showed that p210(BCR-ABL) transfected cells failed to s
urvive after IL-3 removal. Moreover, inhibition of cellular growth was
shown following treatment of p210(BCR-ABL) transformed DA1 cells by p
65 antisense oligonucleotides. This study suggests that p65 NF-kappa B
may be an effector for p210(BCR-ABL) and probably contributes to its
induced transformation process.