Farnesol induces thyroid hormone receptor (THR) {beta}1 but inhibits THR-mediated signaling in MCF-7 human breast cancer cells
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ont., M5S 3E2 (Canada)
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ont., M5S 3E2 (Canada) and Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ont., M5S 3E2 (Canada)
Anti-cancer effects of farnesol are well established, although mechanisms mediating these effects are not fully understood. Since farnesol has been shown to regulate gene transcription through activation of the farnesoid X receptor and the peroxisome proliferator-activated receptors-{alpha} and -{gamma}, we hypothesized that farnesol may also mediate some of its effects through other nuclear hormone receptors. Here we showed that in MCF-7 human breast cancer cells, farnesol induced the expression of thyroid hormone receptor (THR) {beta}1 mRNA and protein at concentrations that inhibited cell growth. Changes in the expression of THR responsive genes, however, suggested that farnesol inhibits THR-mediated signaling. Protein extracts from cells treated with farnesol displayed decreased binding to oligodeoxynucleotides containing a consensus sequence for the THR response element, despite the higher THR{beta}1 content, providing a mechanism to explain the decreased transcriptional activity of cellular THRs.
- OSTI ID:
- 20798924
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 343, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2006.02.145; PII: S0006-291X(06)00454-2; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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