Silencing of TGase 2 sensitizes breast cancer cells to apoptosis by regulation of survival factors

Front Biosci (Landmark Ed). 2009 Jan 1;14:2514-21. doi: 10.2741/3394.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Base Sequence
  • Blotting, Western
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • GTP-Binding Proteins / antagonists & inhibitors
  • GTP-Binding Proteins / genetics*
  • Gene Silencing*
  • Humans
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Small Interfering
  • Transglutaminases / antagonists & inhibitors
  • Transglutaminases / genetics*
  • bcl-X Protein / metabolism

Substances

  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • bcl-X Protein
  • transglutaminase 2
  • Transglutaminases
  • GTP-Binding Proteins