Abstract
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-κBα, leading to inactivation of NF-κB. 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-κB activation.
Original language | English (US) |
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Pages (from-to) | 2514-2521 |
Number of pages | 8 |
Journal | Frontiers in Bioscience |
Volume | 14 |
Issue number | 7 |
DOIs | |
State | Published - Jan 1 2009 |
Externally published | Yes |
Keywords
- I-κBα
- NF-κB
- TGase 2
- siRNA
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology