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


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

9 Figures and Tables

Citations per Year

378 Citations

Semantic Scholar estimates that this publication has 378 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@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} }