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

Willhauck, Michael J.; Sharif-Samani, Bibi; Senekowitsch–Schmidtke, Reingard; Wunderlich, Nathalie; Göke, Burkhard; Morris, John C.; Spitzweg, Christine

doi:10.1007/s10549-007-9646-0

Cited by 29 publications

(31 citation statements)

References 46 publications

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“…In breast cancer cells, many authors reported that retinoic acid is a powerful enhancer of NIS expression especially in association with corticosteroids [12][13][14]. Furthermore, in one report it was also observed that retinoic acid and dexamethasone treatment determined a significant 131 I-induced cytotoxicity in breast cancer cells [15].…”

Section: Introductionmentioning

confidence: 98%

The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS)

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Marano

et al. 2010

Breast Cancer Res Treat

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International audienceNew drugs with anti-tumor activity, also able to modify the expression of selected molecules, are under evaluation in breast cancer which is becoming resistant to conventional treatment, or in metastatic disease. The sodium-iodide symporter (NIS), which mediates iodide uptake into thyroid cells, and is the molecular basis of radioiodine imaging and therapy in thyroid cancer, is also expressed in a large portion of breast tumors. Since NIS expression in breast cancer is not sufficient for a significant iodide uptake, drugs able to induce its expression and correct function are under evaluation. In the present study, we report for the first time that the pan-deacetylase (DAC) inhibitor LBH589 (panobinostat) significantly induced NIS, both as mRNA and as protein, through the increase of NIS promoter activity, with the final consequence of obtaining a significant up-take of iodide in MCF7, T47D, and MDA-MB231 breast cancer cells. Moreover, we observed that LBH589 causes a significant reduction in cell viability of estrogen-sensitive and -insensitive breast cancer cells within nanomolar range. The anti-tumor effect of LBH589 is sustained by apoptosis induction and cell cycle arrest in G/M. In conclusion, our data suggest that LBH589 might be a powerful tool in the management of breast cancer due to its multiple effects and support a potential application of LBH589 in the diagnosis and treatment of this disease

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Section: Introductionmentioning

confidence: 98%

The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS)

Fortunati

Catalano

Marano

et al. 2010

Breast Cancer Res Treat

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“…Administration of dexamethasone (Dex), and carbamazepine (CBZ) together with tRA increased both iodide uptake by NIS, and NIS mRNA expression even more. In response to Dex and CBZ administration, tRA induced I -uptake via NIS have increased about 12 fold in xenograft tumours in experimental animals, clearly indicating that the combination of an RAR isoform selective ligand and Dex and Cbz has a potential to provide a more effective induction of NIS, and it provides an important improvement for the effective use of symporter in theraputic/diagnostic medical approaches (Kogai et al, 2005;Willhauck et al, 2008;.…”

Section: Modulation Of Nis Expression In Breast Cancer Cell Models Anmentioning

confidence: 99%

Regulation of the Functional Na+/I- Symporter (NIS) Expression in Breast Cancer Cells

Tazebay¹

2011

Breast Cancer - Recent Advances in Biology, Imaging and Therapeutics

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“…Moreover, we were able to confirm these results in vivo in MCF-7 xenotransplants, which accumulated approx. 3-5% of the injected dose 123 I per gram tumor (% ID/g) after systemic atRA and Dex treatment as shown by gamma camera imaging [15]. However, although a significant iodide uptake activity was induced by atRA and Dex in vivo an additional stimulation of NIS expression is desirable to enhance sensitivity and efficacy of diagnostic and therapeutic application of radioiodine in breast cancer.…”

Section: Mcf-7 Cells In Vitromentioning

confidence: 99%

“…In more recent studies, we and others have demonstrated that dexamethasone (Dex) is able to significantly enhance atRA-induced NIS expression and iodide accumulation in MCF-7 cells in vitro and in vivo [10,[13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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

Willhauck

O’Kane

Wunderlich

et al. 2010

Breast Cancer Res Treat

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Incubation with CBZ stimulated atRA-induced iodide accumulation up to 2-fold in a concentration-dependent manner, while atRA/Dex-stimulated iodide uptake was further stimulated up to 1.5-fold by additional CBZ treatment based on significantly increased NIS mRNA and protein levels. This stimulatory effect of CBZ was shown to be dependent on the PI3K-Akt pathway without involvement of mTOR. In contrast, treatment with CBZ alone had no effect on functional NIS expression. Moreover, selective cytotoxicity of 131 I was significantly increased from approximately 20 % in MCF-7 cells treated with atRA alone to 50% after treatment with CBZ in the presence of atRA, which was further enhanced to 90% after combined treatment with atRA/Dex/CBZ.In conclusion, CBZ represents another potent stimulator of atRA-induced functional NIS expression resulting in an enhanced selective killing effect of 131 I in MCF-7 breast cancer cells.3

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

Cited by 29 publications

References 46 publications

The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS)

The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS)

Regulation of the Functional Na+/I- Symporter (NIS) Expression in Breast Cancer Cells

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

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