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p27 kip1 overexpression promotes paclitaxel‐induced apoptosis in pRb‐defective SaOs‐2 cells
Author(s) -
Gabellini Chiara,
Pucci Bruna,
Valdivieso Paola,
D'Andrilli Giuseppina,
Tafani Marco,
De Luca Antonio,
Masciullo Valeria
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20900
Subject(s) - transfection , apoptosis , cyclin dependent kinase , paclitaxel , annexin , cell cycle , microbiology and biotechnology , kinase , chemistry , cancer research , cell culture , biology , biochemistry , cancer , genetics
p27 kip1 is a cyclin‐dependent kinase (CDK) inhibitor, which controls several cellular processes in strict collaboration with pRb. We evaluated the role of p27 kip1 in paclitaxel‐induced apoptosis in the pRb‐defective SaOs‐2 cells. Following 48 h of exposure of SaOs‐2 cells to 100 nM paclitaxel, we observed an increase in p27 kip1 expression caused by the decrease of the ubiquitin‐proteasome activity. Such increase was not observed in SaOs‐2 cells treated with the caspase inhibitors Z‐VAD‐FMK, suggesting that p27 kip1 enhancement at 48 h is strictly related to apoptosis. Finally, we demonstrated that SaOs‐2 cells transiently overexpressing the p27 kip1 protein are more susceptible to paclitaxel‐induced apoptosis than SaOs‐2 cells transiently transfected with the empty vector. Indeed, after 48 h of paclitaxel treatment, 41.8% of SaOs‐2 cells transiently transfected with a pcDNA3‐p27 kip1 construct were Annexin V‐positive compared to 30.6% of SaOs‐2 cells transfected with the empty vector ( P < 0.05). In conclusion, we demonstrated that transfection of the pRb‐defective SaOs‐2 cells with the p27 kip1 gene via plasmid increases their susceptibility to paclitaxel‐induced apoptosis. The promoting effect of p27 kip1 overexpression on apoptosis makes p27 kip1 and proteasomal inhibitors interesting tools for therapy in patients with pRb‐defective cancers. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.