期刊
FRONTIERS IN BIOSCIENCE-LANDMARK
卷 14, 期 -, 页码 2514-2521出版社
BIOSCIENCE RESEARCH INST-BRI
DOI: 10.2741/3394
关键词
siRNA; TGase 2; NF-kappa B; I-kappa B kappa; BCl2
资金
- National Cancer Center of Korea [NCC0510270, NCC0810181]
The cross-linking enzyme, Transglutaminase 2 (TGase 2), contributes to physiological homeostasis and plays a role in cell death and survival. We previously showed that down-regulation of TGase 2 by cystamine or synthetic peptide R2 promotes apoptosis in drug-resistant cancer cells by restoring the level of I-kappa B kappa, leading to inactivation of NF-kappa B. To better define the action of TGase 2, its expression was blocked by small interfering RNA. This interference rendered, the doxorubicin-resistant breast cancer cells, highly susceptible to doxorubicin-induced apoptosis. This susceptibility, was associated with decreased levels of the cell-survival factors BCl2 and BCLXL whereas the level of BAX remained un-changed. Together, the findings support the view that TGase 2 leads to drug-resistance by up-regulating the level of survival factors via NF-kappa B activation.
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