EID3
EP300-interacting inhibitor of differentiation 3 (EID-3) (E1A-like inhibitor of differentiation 3) (EID-1-like inhibitor of differentiation 3) (Non-structural maintenance of chromosomes element 4 homolog B) (NS4EB) (Non-SMC element 4 homolog B)
Publications[править]
Previous studies have shown that BMS-345541 (BMS, a specific IκB kinase β inhibitor) sensitized various tumor cells including MCF-7 breast cancer cells to ionizing radiation (IR). However, the mechanisms of BMS action are unknown. Since the expression of E1A-like inhibitor of differentiation 3 (EID3) was highly upregulated in MCF-7 cells after BMS treatment, we investigated the role of EID3 in the response of MCF-7 cells to IR. We found that BMS induced EID3 expression in MCF-7 cells in a time- and dose-dependent manner. Knockdown of EID3 by specific shRNA attenuated BMS-induced radiosensitization in MCF-7 cells. In contrast, induction of EID3 expression in an inducible EID3 expressing MCF-7 cell line with doxycycline sensitized the cells to IR. EID3-mediated sensitization of MCF-7 cells to IR was not attributed to an increase in apoptosis. Instead, EID3-expressing MCF-7 cells exhibited significantly higher levels of senescence associated β-galactosidase (SA-β-gal) activity and higher levels of p21 and p57 than EID3-MCF-7 cells without induction of EID3 after exposure to IR. Similar findings were observed when EID3-expressing MCF-7 cells were treated with etoposide, a topoisomerase II inhibitor. Taken together, our findings reveal a novel function of EID3 and suggest that the induction of EID3 by BMS may be exploited as a new strategy to sensitize breast cancer cells to IR and chemotherapy by inducing cancer cell senescence.
MeSH Terms
- Breast Neoplasms
- Carrier Proteins
- Cellular Senescence
- Cyclin-Dependent Kinase Inhibitor Proteins
- DNA Damage
- DNA Repair
- Etoposide
- Female
- Gene Expression Regulation, Neoplastic
- Gene Knockdown Techniques
- HEK293 Cells
- Humans
- Imidazoles
- MCF-7 Cells
- Quinoxalines
- Radiation, Ionizing
- Radiation-Sensitizing Agents
- Time Factors
- Up-Regulation
Keywords
- Chemotherapy
- EID3
- Ionizing
- MCF-7 breast cancer cells
- Radiation
- Senescence