PT  - JOURNAL ARTICLE
AU  - V. Bourgarel-Rey
AU  - S. Vallee
AU  - O. Rimet
AU  - S. Champion
AU  - D. Braguer
AU  - A. Desobry
AU  - C. Briand
AU  - Y. Barra
TI  - Involvement of Nuclear Factor κB in c-Myc Induction by Tubulin Polymerization Inhibitors
AID  - 10.1124/mol.59.5.1165
DP  - 2001 May 01
TA  - Molecular Pharmacology
PG  - 1165--1170
VI  - 59
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/59/5/1165.short
4100  - http://molpharm.aspetjournals.org/content/59/5/1165.full
SO  - Mol Pharmacol2001 May 01; 59
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.