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- Title
Interferon-regulatory factor-1 is critical for tamoxifen-mediated apoptosis in human mammary epithelial cells.
- Authors
Bowie, Michelle L; Dietze, Eric C; Delrow, Jeffery; Bean, Gregory R; Troch, Michelle M; Marjoram, Robin J; Seewaldt, Victoria L
- Abstract
Unlike estrogen receptor-positive (ER(+)) breast cancers, normal human mammary epithelial cells (HMECs) typically express low nuclear levels of ER (ER poor). We previously demonstrated that 1.0?µM tamoxifen (Tam) promotes apoptosis in acutely damaged ER-poor HMECs through a rapid,‘nonclassic’signaling pathway. Interferon-regulatory factor-1 (IRF-1), a target of signal transducer and activator of transcription-1 transcriptional regulation, has been shown to promote apoptosis following DNA damage. Here we show that 1.0?µM Tam promotes apoptosis in acutely damaged ER-poor HMECs through IRF-1 induction and caspase-1/3 activation. Treatment of acutely damaged HMEC-E6 cells with 1.0?µM Tam resulted in recruitment of CBP to the?-IFN-activated sequence element of the IRF-1 promoter, induction of IRF-1, and sequential activation of caspase-1 and -3. The effects of Tam were blocked by expression of siRNA directed against IRF-1 and caspase-1 inhibitors. These data indicate that Tam induces apoptosis in HMEC-E6 cells through a novel IRF-1-mediated signaling pathway that results in activated caspase-1 and -3.Oncogene (2004) 23, 8743-8755. doi:10.1038/sj.onc.1208120 Published online 4 October 2004
- Subjects
APOPTOSIS; EPITHELIAL cells; TAMOXIFEN; ESTROGEN antagonists; BREAST cancer; GENETIC mutation
- Publication
Oncogene, 2004, Vol 23, Issue 54, p8743
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1208120