Caspase-3 inhibits the growth of breast cancer cells independent of protease activity

✍ Scribed by Beatrice Faraglia; Alessia Bonsignore; Franco Scaldaferri; Alma Boninsegna; Achille Cittadini; Cesare Mancuso; Alessandro Sgambato

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 151 KB
• Volume: 202
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20149

✦ Synopsis

Abstract

In this study, the MCF‐7 breast cancer cells that lack caspase‐3 were transfected with a wild type (WT) or mutant caspase‐3 cDNA. Expression of the WT, but not of the mutant, caspase‐3 was associated with increased caspase activity and susceptibility to staurosporine (STS)‐induced apoptosis. Both derivatives displayed inhibition of cell growth compared with vector control cells. Growth inhibition was associated with increased expression of the cyclin dependent kinase (CDK) inhibitor p27^Kip1^ in the WT, but not in the mutant caspase‐3 expressing cells. Cyclin D1 expression level was not affected by caspase‐3 expression. Phosphorylation of the Akt protein was decreased in both WT and mutant caspase transfected cells, although Akt expression level remained unchanged. These results suggest that caspase‐3 might have biological functions independent of its protease activity and that its loss might contribute to tumor development by increasing the growth potential of cancer cells. © 2004 Wiley‐Liss, Inc.