The effect of retinoic acid on sodium-iodide symporter gene (NIS) expression in breast cancer and normal breast cells

M Jarzab, MD a, V Piddubnyak, MSc a, J Szary, PhD b, B Maka, MD, PhD c, M Wiench, PhD d, B Nikiel, MSc e, A Goraj-Zajac, MSc e, K Lisowska, PhD a, Z Krawczyk, PhD a

Dept. of Tumor Biology a, Molecular Biology b, Surgery c, Nuclear Medicine and Endocrine Oncology d, Pathology e, Centre of Oncology -- Maria Sklodowska-Curie Memorial Institute, Gliwice Branch, Poland, e-mail:

AIM: Sodium-iodide symporter (NIS) is a membrane protein necessary for iodine uptake. Its induction in breast cancer cells may enable therapeutic approach with sterilizing doses of radioiodine. The aim of our study was to evaluate the ability of redifferentiation treatment with retinoic acid to induce sodium-iodide symporter expression in breast cancer cells, and to verify the cellular localization of NIS protein in breast cancer cells. METHODS: We have analyzed two established cell lines MCF-7 (breast cancer), MCF-10A (benign disease) and paired breast cancer/normal breast tissue primary cell lines obtained from excised human tumors. NIS expression was analyzed by RT-PCR and quantitative real-time PCR (TaqMan, ABI 7700). To analyze expression of NIS at a cellular level, MCF-7 cells were stably transfected with NIS gene and analyzed by immunohistochemistry. RESULTS: A low basal NIS expression was found in MCF-7 and MCF-10A cells. Retinoic acid increased NIS expression only in MCF-7 breast cancer cells, in contrast to MCF-10A normal cells. In MCF-7 cells stably transfected with NIS gene, we have showed by immunohistochemistry the membrane localization of NIS protein. In the first analyzed pair of breast cancer/normal tissue primary cell lines there was no noticeable increase of basal NIS expression after retinoic acid stimulation. These results will be extended and completed by quantitative PCR. CONCLUSIONS: We have confirmed the potential of retinoic acid to stimulate NIS expression in MCF-7 cancer cell line, opposite to cell lines from benign breast disease.

KEY WORDS: sodium-iodide symporter, retinoic acid, breast cancer.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Novel Therapies, Part 1.