크레아틴 인산화효소 B 에 의한 TGF-β 신호전달 조절

Abstract

Creatine kinase B (CKB) is a cytosolic isoform of creatine kinase that regulates energy homeostasis at high level of energy demanded sites. To identify the effect of CKB in breast cancer cells, I overexpressed CKB to CKB low MDA-MB-231 cells. The overexpression of CKB resulted in increase resistance to drug treatment, UV radiation and energy stresses. Transforming growth factor beta (TGF-β) has tumor-suppressive effects such as differentiation, apoptosis in normal cells. However, it is causally related with cancer progression in malignant cancer cells. When the effect of CKB on TGF-β signaling was examined, the cells were treated with TGF-β treatment increased the basal phosphorylation level of Smad2, an indicator of TGF-β signaling activation, was up-regulated in MDA-MB-231 CKB cells compared to MDA-MB-231 vec cells. I also identified that TGF-β considerably enhanced cell viability and decreased doxorubicin-induced apoptosis during doxorubicin treatment in MDA-MB-231 CKB cells. These results suggest that CKB overexpression attenuates various stress-induced apoptosis and potentiates their resistant ability by enhancement of TGF-β signaling in MDA-MB-231 cells.