Effect of Ligands of Nuclear Hormone Receptors on Sodium/Iodide Symporter Expression and Activity in Breast Cancer Cells

Abstract

Iodide uptake by normal and cancerous thyroid cells is an active process mediated by the sodium/iodide symporter (NIS). Using quantitative real-time RT-PCR, we found that all 22 fresh human breast cancer samples had very low NIS expression similar to levels in untreated MCF-7 breast cancer cells. 9-cis retinoic acid (9-cis RA), a ligand for both retinoic acid receptor (RAR)/retinoic X receptor (RXR) heterodimers as well as RXR/RXR homodimers, markedly induced NIS mRNA expression in MCF-7 breast cancer cells in a dose- and time-dependent fashion, with maximal levels occurring at 12 h. All-trans retinoic acid, ATRA, a RAR specific ligand had a similar potency. Among eight breast cancer cell lines, three out of four estrogen receptor (ER)-positive and zero of four ER-negative cell lines responded to 9-cis RA by increasing their expression of NIS. Combining a RAR with a RXR selective ligand enhanced both NIS mRNA expression and iodide uptake in MCF-7 cells. Similarly, a ligand for proliferator-activated receptor γ (PPARγ) when combined with 9-cis RA synergistically increased both NIS mRNA levels and iodide uptake in these MCF-7 cells. The iodide uptake was blocked by KClO4. In conclusions, these findings suggest that selected combinations of NHR ligands should be examined in a limited trial to determine if their administration to patients allows the use of radioactive iodine for diagnosis and possibly treatment of metastatic breast cancer.

DOI: 10.1023/A:1024064424855

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@article{Tanosaki2003EffectOL, title={Effect of Ligands of Nuclear Hormone Receptors on Sodium/Iodide Symporter Expression and Activity in Breast Cancer Cells}, author={Sakae Tanosaki and Takayuki Ikezoe and Anthony Patrick Heaney and Jonathan Said and Kazuo Dan and Makoto Akashi and H Phillip Koeffler}, journal={Breast Cancer Research and Treatment}, year={2003}, volume={79}, pages={335-345} }