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Title: Tamoxifen enhancement of TNF-α induced MnSOD expression: Modulation of NF-κB dimerization
Authors: Chotiros Daosukho
Kelley Kiningham
Edward J. Kasarskis
Wanida Ittarat
Daret K. St. Clair
University of Kentucky College of Medicine
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jan-2002
Citation: Oncogene. Vol.21, No.22 (2002), 3603-3610
Abstract: Manganese superoxide dismutase (MnSOD) has been shown to suppress the development of cancer. Tamoxifen (TAM), a nonsteroidal anti-estrogen that is widely used in chemotherapy, is known to be a modulator of antioxidant status. However, the mechanism by which TAM mediates antioxidant enzyme induction remains unclear. In this study we investigated TAM enhancement of MnSOD induction by TNF-α. The results show that co-treatment with TAM and TNF-α increases the MnSOD promoter/enhancer driven luciferase activity, MnSOD mRNA and protein levels. Interestingly, co-treatment with TAM and TNF-α drastically decreases the binding activity of the p50/p50 homodimer and increases that of the p50/p65 heterodimer compared to TNF-α alone. This change in DNA binding could not be attributed to a decrease in the level of p50, its precursor, p105, or its inhibitors. Furthermore, TAM did not enhance degradation of IκB-α. These results suggest that p50/p50 homodimer may act as an inhibitory complex of MnSOD expression. Modulation of the DNA binding activity in favor of the p50/p65 complex may enhance NF-κB mediated induction of MnSOD by TAM. These findings reveal a potential novel mechanism for the induction of the human MnSOD gene.
ISSN: 09509232
Appears in Collections:Scopus 2001-2005

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