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Farnesol induces thyroid hormone receptor beta 1 in MCF‐7 cells but decreases expression of thyroid hormone receptor beta1‐regulated genes
Author(s) -
Duncan Robin Elaine,
Archer Michael C.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a560-c
Subject(s) - farnesol , thyroid hormone receptor , nuclear receptor , medicine , endocrinology , receptor , thyroid hormone receptor beta , chemistry , hormone receptor , biology , retinoid x receptor alpha , retinoid x receptor , thyroid , transcription factor , biochemistry , gene , cancer , breast cancer
Farnesol is produced endogenously in cells as a metabolite of the mevalonate/cholesterol biosynthetic pathway, and is also consumed in dietary fruits and vegetables. Anti‐cancer effects of farnesol are well established, although mechanisms mediating these effects are not fully understood. Farnesol has previously been shown to regulate activity of the farnesoid X receptor, and peroxisome proliferator‐activated receptors alpha and gamma. We hypothesized that farnesol may mediate some of its effects through regulation of other members of the steroid/thyroid nuclear receptor superfamily of ligand‐activated transcription factors. We examined the effect of farnesol on thyroid hormone receptor (THR) beta 1 and found increased protein and mRNA expression at concentrations that inhibited MCF‐7 cell growth. No effect of farnesol was observed on THR alpha 1 or retinoid X receptor beta mRNA. Measurement of mRNA expression of genes known to be regulated by THR beta 1 (including Spot 14, the sodium iodide symporter, and carnitine palmitoyl transferase Ia) strongly suggested, however, that farnesol decreased activity of this nuclear hormone receptor. We conclude that farnesol induces THR beta 1 but appears to decrease signalling by this transcription factor.