Silencing of TGase 2 sensitizes breast cancer cells to apoptosis by regulation of survival factors.
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-kBa, leading to inactivation of NF-kB. 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-kB activation.
Kim
Dae-Seok
DS
Molecular Oncology Branch, Division of Basic and Applied Science, Research Institute, National Cancer Center, Goyang, Kyonggi-do, Republic of Korea.
Park
Kang-Seo
KS
Kim
Soo-Youl
SY
D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D020868:Gene Silencing; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000235:genetics*; D051020:bcl-X Protein / Q000378:metabolism
D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051020:bcl-X Protein; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins