Stimulation of retinoic acid-induced functional sodium iodide symporter (NIS) expression and cytotoxicity of 131I by carbamazepine in breast cancer cells

  title={Stimulation of retinoic acid-induced functional sodium iodide symporter (NIS) expression and cytotoxicity of 131I by carbamazepine in breast cancer cells},
  author={Michael J. Willhauck and D. Okane and Nathalie Wunderlich and Burkhard Göke and Christine Spitzweg},
  journal={Breast Cancer Research and Treatment},
The sodium iodide symporter (NIS) mediates the active iodide uptake in the thyroid gland as well as lactating breast tissue. Recently, we reported significant stimulation of all-trans retinoic acid (atRA)-induced NIS expression in the estrogen-receptor positive human breast cancer cell line MCF-7 by dexamethasone (Dex) in vitro and in vivo, which might offer the potential to image and treat breast cancer with radioiodine. In this study, based on its known interaction with the pregnane-X… 

The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue

The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammaries NIS mediated by thyroid hormones.

Title The Sodium Iodide Symporter ( NIS ) and Potential Regulatorsin Normal , Benign and Malignant Human Breast Tissue

Although NIS expression is significantly higher in malignant compared to normal breast tissue, the highest level was detected in fibroadenoma, and the data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammaries NIS mediated by thyroid hormones.

The sodium iodide symporter (NIS): regulation and approaches to targeting for cancer therapeutics.

ATRA increases iodine uptake and inhibits the proliferation and invasiveness of human anaplastic thyroid carcinoma SW1736 cells: Involvement of β-catenin phosphorylation inhibition

ATRA could be used to improve the isotope sensitivity of ATC by increasing the iodine uptake and inhibited the proliferation and invasion of SW1736 cells, involving β-catenin phosphorylation.

The sodium/iodide symporter NIS is a transcriptional target of the p53-family members in liver cancer cells

Results indicate that the NIS gene is a direct target of the p53 family and suggests that the modulation of NIS by DNA-damaging agents is potentially exploitable to boost NIS upregulation in vivo.

Pregnane X receptor and human malignancy.

PXR down-regulation could be considered as a novel therapeutic approach to overcome chemoresistance, while future research should be mainly focused on modulating PXR status in order to increase chemotherapy effectiveness and finally improve cancer patient prognosis.

Palmitic Acid Downregulates Thyroglobulin (Tg), Sodium Iodide Symporter (NIS), and Thyroperoxidase (TPO) in Human Primary Thyrocytes: A Potential Mechanism by Which Lipotoxicity Affects Thyroid?

The results demonstrated that upon palmitic acid stimulation, the expressions of the key molecules (thyroglobulin, sodium iodide symporter, and thyroperoxidase) were reduced and their activities were suppressed, which might lead to impaired thyroid hormone synthesis.

Sodium iodide symporter (NIS) in extrathyroidal malignancies: focus on breast and urological cancer

This review describes recent findings in NIS research in extrathyroidal malignancies, focusing on breast and urological cancer, emphasizing the most relevant developments that may have clinical impact.

Expression of sodium iodide symporter in human breast tissues.

NIS expression appeared to be independent of estrogen (ER) and progesterone receptor (PR) expression as well as of lymph node status, and the hypothesis of the downregulation of NIS expression during carcinogenesis cannot be excluded.

Sodium Iodide Symporter for Nuclear Molecular Imaging and Gene Therapy: From Bedside to Bench and Back

The diagnostic and therapeutic applications of NIS as a radionuclide-based reporter gene for trafficking cells and a therapeutic gene for treating cancers are demonstrated.



Dexamethasone stimulation of retinoic Acid-induced sodium iodide symporter expression and cytotoxicity of 131-I in breast cancer cells.

Treatment with Dex in the presence of atRA significantly increases functional NIS expression levels in addition to inhibiting iodide efflux, resulting in an enhanced selective killing effect of 131-I in MCF-7 breast cancer cells.

Differential regulation of sodium/iodide symporter gene expression by nuclear receptor ligands in MCF-7 breast cancer cells.

The addition of Dex reduced the effective dose of retinoid and prolonged the induction of NIS, especially with AGN190168, suggesting higher efficacy of (131)I after combination treatment.

Retinoic acid stimulation of the sodium/iodide symporter in MCF-7 breast cancer cells is mediated by the insulin growth factor-I/phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase signaling pathways.

Despite the chronic inhibitory effects on cell proliferation, tRA did not reduce the S-phase distribution of MCF-7 cells during the period of NIS induction, and the IGF-I receptor/PI3K pathway mediates tRA-stimulated NIS expression in MCf-7 but not FRTL-5 thyroid cells.

Activation of the PI3 kinase pathway by retinoic acid mediates sodium/iodide symporter induction and iodide transport in MCF-7 breast cancer cells.

Findings indicate that RA induction of NIS in MCF-7 cells is mediated by rapid activation of the PI3K pathway and involves direct interaction with RAR and retinoid X receptor.

Functional sodium iodide symporter expression in breast cancer xenografts in vivo after systemic treatment with retinoic acid and dexamethasone

Treatment with Dex in the presence of atRA is able to induce significant amounts of iodide accumulation in breast cancer xenotransplants in vivo due to stimulation of functional NIS protein expression, which opens exciting perspectives for a possible diagnostic and therapeutic role of radioiodine in the treatment of breast cancer.

Retinoic acid induces sodium/iodide symporter gene expression and radioiodide uptake in the MCF-7 breast cancer cell line.

Stimulation of radioiodide uptake after systemic retinoid treatment may be useful for diagnosis and treatment of some differentiated breast cancers.

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

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.

Systemic Retinoic Acid Treatment Induces Sodium/Iodide Symporter Expression and Radioiodide Uptake in Mouse Breast Cancer Models

The in vivo efficacy and specificity of tRA-stimulated iodide accumulation and NIS mRNA and protein induction in mouse breast cancer models demonstrate selective induction of functional NIS in breast cancer by tRA.

Ligands for peroxisome proliferator-activated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice.

The combination of TGZ and ATRA synergistically and irreversibly inhibits growth and induces apoptosis of MCF7 breast cancer cells and the combination may provide a novel, nontoxic and selective therapy for human breast cancers.

Hydrocortisone and purinergic signaling stimulate sodium/iodide symporter (NIS)-mediated iodide transport in breast cancer cells.

It is reported that hydrocortisone and ATP each markedly stimulates tRa-induced NIS protein expression and plasma membrane targeting in MCF-7 cells, leading to at least a 100% increase in iodide uptake, thus improving the feasibility of using radioiodide to effectively treat breast cancer.