Abstract 4972: Phosphorylation of caspase-3 and caspase-7 by p21-activated protein kinase (PAK)2 inhibits chemotherapeutic drug-induced apoptosis of breast cancer cell lines

Abstract

Abstract P21-activated kinase (PAK)2, a member of PAK family of serine/threonine protein kinases, plays an important role in physiological processes such as motility, survival, mitosis, and apoptosis. However, the role of PAK2 in chemotherapy resistance remains unclear. Here we report that PAK2 is highly expressed in human breast cancer cell lines and human breast invasive carcinoma tissue compared with human non-tumorigenic mammary epithelial cell lines and adjacent normal breast tissue respectively. Interestingly, we found that PAK2 can phosphorylate caspase-3 at Thr77, Thr152 and Thr245. Moreover, PAK2 can bind with caspase-7 and phosphorylate caspase-7 at Ser30, Thr173 and Ser239. Functionally, the phosphorylation of caspase-3 and caspase-7 decreases their activity, thereby inhibiting staurosporine and doxorubicin HCl-induced cellular apoptosis. Our data indicate that highly expressed PAK2 mediates chemotherapy resistance in human breast invasive ductal carcinoma by negatively regulating caspase-3 and caspase-7 activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4972. doi:1538-7445.AM2012-4972