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Vol. 59, Issue 5, 1165-1170, May 2001
B in c-Myc Induction by Tubulin
Polymerization Inhibitors
Unité Mixte de Recherche Centre National de la
Recherche Scientifique 6032, Faculté de Pharmacie, Marseille,
France
We showed previously that microtubule disassembly by vinblastine
induces the proto-oncogene c-myc in epithelial mammary HBL100 cells
(Bourgarel-Rey et al., 2000). In this study, we demonstrate that
vinblastine treatment in these cells, in contrast to what was observed
with the colon adenocarcinoma cell line HT29-D4, activated the
transcription factor NF
B, which has been involved in c-myc
regulation. The microtubule disassembly also induced I
B degradation.
Using transient transfection analysis, we show that the
trans-activation of c-myc by vinblastine was decreased when NF
B binding sites on c-myc promoter were mutated. Additionally, we demonstrate that microtubule dissolution
trans-activated a thymidine kinase-CAT construct
containing an NF
B binding site at
1180 to
1080 bp relative to
the P1 promoter. Thus, vinblastine up-regulates the enhancer activity
of the NF
B binding site. These results suggest that microtubule
disassembly induced by vinblastine can trans-activate
the c-myc oncogene through NF
B. Taking into consideration the
paradoxical roles of both c-myc and NF
B in proliferation or
apoptosis, this data reveals the complex action mechanism of this
microtubule interfering agent.
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