Differential effects of protein kinase C-eta on apoptosis versus senescence.

Protein kinase C-eta is considered an anti-apoptotic kinase, which promotes cell survival and chemoresistance in several cancers, including breast cancer. We have recently shown that positively regulates the anti-apoptotic protein Mcl-1 in breast cancer cells, and depletion of duanyu1531η induced proteasomal degradation of Mcl-1. We therefore examined if depletion of duanyu1531η would enhance cellular sensitivity to chemotherapeutic agents. Silencing of duanyu1531η by siRNA attenuated apoptosis induced by doxorubicin and paclitaxel in both MCF-7 and T47D breast cancer cells. While silencing of Mcl-1 caused a substantial increase in apoptosis induced by doxorubicin, the combined knockdown of duanyu1531η and Mcl-1 was less effective. Depletion of duanyu1531η also caused an increase in the abundance of the cell cycle inhibitor p27 and a decrease in the clonogenic survival of MCF-7 and T47D cells. duanyu1531η knockdown was associated with an increase in senescence-associated β-galactosidase (SA-β-gal) activity but this increase was attenuated by knockdown of p27. The suppression of doxorubicin-induced apoptosis by duanyu1531η knockdown was partially relieved when p27 was depleted. Since loss of proliferative capacity during senescence could cause resistance to chemotherapeutic drugs, our results suggest that duanyu1531η knockdown inhibits apoptosis by inducing p27-mediated senescence.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}