Effect of sodium/iodide symporter (NIS)-mediated radioiodine therapy on estrogen receptor-negative breast cancer

Abstract

Since the sodium/iodide symporter (NIS) stimulates the iodine uptake in normal lactating breast, our study aimed to study the effect of NIS-mediated radioiodide therapy on ER-negative breast cancers. A recombinant lentivirus plasmid encoding the human NIS (hNIS) gene and firefly luciferase (Fluc) was constructed. MDA-MB-231 cells were transfected with the recombinant lentivirus, and the hNIS gene expression was identified by western blot analysis and real-time PCR. Tissue-specific expression of the NIS gene was confirmed by immunohistochemical (IHC) staining. Functional NIS activity in the MDA-hNIS cells was confirmed by the uptake of 131I and cytotoxicity assays. The relative expression level of hNIS mRNA exhibited a 10-fold higher expression in the MDA-hNIS cells compared with the level in the control cells without the endogenous NIS gene. Abundant expression of hNIS protein was noted in the cell membrane compared to the cytoplasm which confirmed the efficient expression of the functional hNIS gene. Iodine uptake into the MDA-hNIS cells was rapid, reaching a maximum after 15 min, followed by a decline. Exposure of the MDA-hNIS cells with 131I resulted in a time-dependent reduction in colony formation compared with the survival of the control (MDA) cells. Our results confirmed that NIS overexpression enhances the sensitivity of ER-negative breast cancer cells to radioiodide therapy.

1,25-hydroxyvitamin D3 decreases endoplasmic reticulum stress-induced inflammatory response in mammary epithelial cells

“…Although a general limitation of this study is the use of a transformed human breast cancer cell line, which displays differences from normal MECs with regard to the abundance of certain receptors, such as estrogen receptors [55], and the response to non-physiological (e.g. exogenous retinoic acid) stimuli [56], both MCF-7 cells and normal MECs cells exhibit a similar regulation by important lactogenic hormones including oxytocin and prolactin [57][58][59].…”

Short-term Effects of Radioiodine Therapy on Auditory Function

“…OAEs, also known as Kemp potentials, have widespread clinical applications [19] . The main advantages of OAEs include simplicity, non-invasiveness, and cost-effectiveness [25] . DP-OAEs provide strong evidence of normal cochlear function and have the advantage of reflecting the physiological function of the inner ear more closely than the other types of OAEs [25] .…”

How does radioactive iodine affect the nose?

“…Numerous tissues have cells with this transport mechanism, including the salivary glands, the lacrimal gland, and gastric mucosa. Absorption of RAI by these tissues can lead to sialoadenitis, xerostomia, dry eye, conjunctivitis, epigastric pain, and pulmonary fibrosis . Accumulation of RAI in nasal tissue following administration of a 5‐mCi diagnostic dose and a therapeutic dose of 150 mCi has been reported; however, data on its effect on nasal symptoms and function are limited …”

“…Absorption of RAI by these tissues can lead to sialoadenitis, xerostomia, dry eye, conjunctivitis, epigastric pain, and pulmonary fibrosis. [4][5][6] Accumulation of RAI in nasal tissue following administration of a 5-mCi diagnostic dose and a therapeutic dose of 150 mCi has been reported; however, data on its effect on nasal symptoms and function are limited. 7,8 The nasal mucosa is sensitive to environmental conditions, climactic changes, local and systemic diseases, and drugs.…”