RT Journal Article
SR Electronic
T1 Involvement of Nuclear Factor κB in c-Myc Induction by Tubulin Polymerization Inhibitors
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1165
OP 1170
DO 10.1124/mol.59.5.1165
VO 59
IS 5
A1 V. Bourgarel-Rey
A1 S. Vallee
A1 O. Rimet
A1 S. Champion
A1 D. Braguer
A1 A. Desobry
A1 C. Briand
A1 Y. Barra
YR 2001
UL http://molpharm.aspetjournals.org/content/59/5/1165.abstract
AB 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 NFκB, which has been involved in c-myc regulation. The microtubule disassembly also induced IκB degradation. Using transient transfection analysis, we show that thetrans-activation of c-myc by vinblastine was decreased when NFκB binding sites on c-myc promoter were mutated. Additionally, we demonstrate that microtubule dissolutiontrans-activated a thymidine kinase-CAT construct containing an NFκB binding site at −1180 to −1080 bp relative to the P1 promoter. Thus, vinblastine up-regulates the enhancer activity of the NFκB binding site. These results suggest that microtubule disassembly induced by vinblastine can trans-activate the c-myc oncogene through NFκB. Taking into consideration the paradoxical roles of both c-myc and NFκB in proliferation or apoptosis, this data reveals the complex action mechanism of this microtubule interfering agent.