Farnesol induces thyroid hormone receptor (THR) beta1 but inhibits THR-mediated signaling in MCF-7 human breast cancer cells.
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) beta1 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 THRbeta1 content, providing a mechanism to explain the decreased transcriptional activity of cellular THRs.
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ont., Canada M5S 3E2.
Robin E
RE
Duncan
Michael C
MC
Archer
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D005204:Farnesol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction / Q000187:drug effects; D037042:Thyroid Hormone Receptors beta / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D037042:Thyroid Hormone Receptors beta; D005204:Farnesol; D004247:DNA