p27 kip1 overexpression promotes paclitaxel‐induced apoptosis in pRb‐defective SaOs‐2 cells

• Published in: Journal of cellular biochemistry 2006-08, Vol.98 (6), p.1645-1652
• Main Authors: Gabellini, Chiara, Pucci, Bruna, Valdivieso, Paola, D'Andrilli, Giuseppina, Tafani, Marco, De Luca, Antonio, Masciullo, Valeria
• Format: Article
• Language: English
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.20900

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