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 froth cells treated with farnesol displayed decreased binding to oligode-oxynucleotides 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. (c) 2006, Elsevier Inc. All rights reserved.