Mammary Gland Sodium / Iodide Symporter Expression And Function Of Regulation Of Research

OBJECTIVES1. To study the expression of sodium-iodide symporter (NIS) mRNA and protein in normal and benign or malignant breast tissue, and investigate the association between NIS and breast disease.2. To investigate the effect of steroids, thyrotropin (TSH), triiodothyronine (T3), iodide, and cytokines on the expression of NIS mRNA in breast cancer cells.3. To investigate the effect of retinoic acid (RA), prolactin and leptin on the expression of gene and protein of NIS and the relationship between NIS expression and the ability of iodide uptake in breast cancer cell.METNODS1. Breast tissues were taken at surgery from patients with breast adenoma, nodule of lobuli glandulae mammariae and breast cancer. Normal samples adjacent to breast cancer were used as control. NIS mRNA and protein were assessed in these samples by reverse transcription polymerase chain reaction (RT-PCR), Western blot and immunohistochemistry methods.2. Breast cancer cell lines (MCF-7 and MDA-MB-453) were cultured in the absence or presence of different concentrations of estradiol, progesterone, testosterone, dehydrotestosterone, dehydroepiandrosterone , dexamethasone, TSH, T3, Nal, TNF- a, IFN- r, or IL-6 for 72h. The level of NIS gene expression was assessed by RT-PCR.3. The breast cancer cell line (MCF-7) was cultured with or without different concentrations of RA, PRL or leptin for various times. NIS mRNA and protein in cultured breast cancer cells was determined by RT-PCR, Western blot and immunocytochemistry. The activity of iodide uptake was determined by 125I uptake rate.RESULTS1. NIS mRNA and protein were undetectable in benign breast nodules and normal breast tissues, while they could be found by RT-PCR and Western blot methods in all breast cancer samples, though this protein was found mainly in cytoplasm as detected by immunohistochemistry.2. Estradiol, progesterone, testosterone, TSH and T3 promoted NIS mRNA expression in breast cancer cells in a dose-dependent manner, while dexamethasone, Nal, TNF- a , IFN-r and IL-6 inhibited NIS mRNA in breast cancer cells dose-dependently. Dehydrotestosterone and dehydroepiandrosterone had no effect on the expression of NIS mRNA in these cells.3. NIS gene expression was enhanced by RA, PRL or leptin in a dose- and time-dependent manner. RA, PRL or leptin also dose-dependently up-regulated NIS protein expression. The activity of iodide uptake had been found to be increased by RA and leptin, whereas there was no effect of prolactin.CONCLUSIONExpression of NIS gene and protein in breast cancer could be regulated by many kinds of factors including steroids, thyrotropin, triiodothyronine, sodium iodide, TNF- a, IFN- y , IL-6, retinoic acid, prolactin, and leptin. But only RA and leptin could increase iodide-uptake in breast cancer cell because the resumption of the ability of iodide-uptake needs NIS protein normal function. The decreased ability of iodide uptake by breast cancer might result from the defect of NIS mRNA on translational or post-translational pathways.