K. Makino et al., Transcriptional upregulation and activation of p55Cdc via p34(cdc2) in Taxol-induced apoptosis, ONCOGENE, 20(20), 2001, pp. 2537-2543
Paclitaxel (Taxol) is a potent and highly effective antineoplastic agent fo
r the treatment of advanced, drug-refractory, metastatic breast cancers. Ta
xol not only induces tubulin polymerization, stabilizes microtubules, block
s cell cycle progression, and induces apoptosis, but it also alters gene ex
pression. Here, we have identified that Taxol can upregulate expression of
the gene encoding the cell cycle protein p55Cdc by using cDNA array techniq
ue. Taxol induced p55Cdc mRNA expression through activation of the p55Cdc p
romoter, which led to increase p55Cdc protein expression. Taxol also activa
ted p55Cdc-associated kinase, In addition, overexpression of the p55Cdc gen
e resulted in cell death in both HeLa cells and NIH3T3 cells in a dose-depe
ndent manner. A dominant-negative mutant of p34(cdc2) blocked Taxol-induced
p55Cdc activation and inhibited p55Cdc-induced and Taxol-induced cell deat
h. Our data suggest that transcriptional upregulation of p55Cdc and activat
ion of p55Cdc by Taxol-mediated p34(cdc2) activation play a critical role i
n Taxol-induced cell death.