Can deacetylation promote radioiodide uptake in thyroid cancer?
C Clarke, E Burbridge & PPA Smyth
Acetylation of DNA can result in gene silencing. In the thyroid such phenomena can lead to the loss of ability to accumulate radioiodide. The aim of this study was to examine the effects on the rat thyroid cell line FRTL-5 and human thyroid follicular cancer cell line FTC-133 of Trichostatin A (TSA), a histone deactylase inhibitor. A concentration of TSA was selected using MTT cell viability assays for use in uptake, efflux and expression studies. Cells were incubated with TSA [2.5-50ng/ml] for 72 hours followed by 125I for 4 hours after which uptake or timed efflux of 125I was measured. TSA caused a decrease in uptake [2.5-50ng/ml] in FRTL-5 cells. Efflux was also diminished [2.5-50ng/ml] in a dose dependent manner. Thyroidal expression of the human Sodium iodide symporter (NIS), human apical iodide transporter (hAIT) and Pendrin (PDS) DNA.iodide transporters was determined by semi quantitative RT-PCR. NIS levels were unaffected while PDS decreased with increasing concentration of TSA. NIS and hAIT, whose expression was absent in the FTC-133 cell line, was induced after 24 hours in the presence of TSA. PDS, which is expressed in the FTC-133 cell line, was unaffected by TSA. It is concluded that the effect of TSA in promoting 125I retention (decreased efflux) has the potential of increasing the effectiveness of 131I ablative therapy. In addition, TSA could be used therapeutically for the redifferentiation of thyroid cancers to promote radioiodide uptake.