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

Guerrieri, F.; Piconese, Silvia; Lacoste, Claire; Schinzari, Valeria; Testoni, Barbara; Valogne, Yannick; Gerbal‐Chaloin, Sabine; Samuel, Didier; Bréchot, Christian; Levrero, Massimo

doi:10.1038/cddis.2013.302

Cited by 19 publications

(21 citation statements)

References 59 publications

(85 reference statements)

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“…These results were then confirmed in in vitro studies, and a recent study in a human extrahepatic CC cell line shows that these cells also overexpress NIS [27,28]. NIS has a key role in metabolic radiotherapy, using iodine-131, for the treatment of thyroid tumors, being also currently under active investigation for the treatment of extrathyroidal tumors.…”

Section: Molecular and Genetic Alterationssupporting

confidence: 65%

Cholangiocarcinoma: from molecular biology to treatment

et al. 2015

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Cholangiocarcinoma is a rare tumor originating in the bile ducts, which, according to their anatomical location, is classified as intrahepatic, extrahepatic and hilar. Nevertheless, incidence rates have increased markedly in recent decades. With respect to tumor biology, several genetic alterations correlated with resistance to chemotherapy and radiotherapy have been identified. Here, we highlight changes in KRAS and TP53 genes that are normally associated with a more aggressive phenotype. Also IL-6 and some proteins of the BCL-2 family appear to be involved in the resistance that the cholangiocarcinoma presents toward conventional therapies. With regard to diagnosis, tumor markers most commonly used are CEA and CA 19-9, and although its use isolated appears controversial, their combined value has been increasingly advocated. In imaging terms, various methods are needed, such as abdominal ultrasound, computed tomography and cholangiopancreatography. Regarding therapy, surgical modalities are the only ones that offer chance of cure; however, due to late diagnosis, most patients cannot take advantage of them. Thus, the majority of patients are directed to other therapeutic modalities like chemotherapy, which, in this context, assumes a purely palliative role. Thus, it becomes urgent to investigate new therapeutic options for this highly aggressive type of tumor.

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Section: Molecular and Genetic Alterationssupporting

confidence: 65%

Cholangiocarcinoma: from molecular biology to treatment

et al. 2015

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“…In thyroid cancers, NIS expression is mainly controlled by the transcription factors Pax-8 and Nkx2.1, which target the upstream enhancer (NUE), and by the cardiac homeobox transcription factor Nkx2.5, which regulates the activity of the NIS core promoter [9,[37][38][39]. Recently, in liver cancer cells, p53 was shown to mediate transcriptional activation of the NIS in response to DNA damage, triggering DNA damage-induced apoptosis [30]. Previous studies have shown that a higher frequency of mutations in p53 in ATC [40] and p53 plays an important role in developing ATC [41].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that NIS expression is regulated by several transcription regulators [30], we examined whether wild-type p53 upregulates NIS expression through binding to NIS promoter in ATC cells. The ability of wild-type p53 to regulate NIS promoter activity was investigated by a luciferase promoter reporter assay.…”

Section: Wild-type P53 Induces Nis Expression In Atc Cellsmentioning

confidence: 99%

“…Cell transfection and luciferase promoter reporter assay [25] Cell transfections with the indicated luciferase reporter, expression vectors encoding wild-type p53 or NIS and Renilla luciferase pRL null vector were performed using TransIT-TKO and TransIT-LT1 reagents from Mirus (Mirus Bio LLC, Madison, WI, USA). Cells were transiently transfected with either the wild-type p53-containing expression vector or the Renilla luciferase pRL null vector (pRL-CMV; Promega, Madison, WI, USA), used to correct for transfection efficiency.…”

Section: Western Blot Analysismentioning

confidence: 99%

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Wild-Type P53 Induces Sodium/Iodide Symporter Expression Allowing Radioiodide Therapy in Anaplastic Thyroid Cancer

Liu¹,

Chen

et al. 2017

Cell Physiol Biochem

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Aims: Anaplastic thyroid cancer(ATC) is one of the most aggressive solid tumors. Mutations in the p53 gene are common in anaplastic thyroid cancer, but the effects of p53 mutations are yet to be elucidated. Here, we investigated the role of p53 in ATC. Methods: p53 mutation was detect by immunohistochemistry in ATC tissues. Expression of NIS were measured using immunohistochemistry, qRT-PCR, western blot, immunofluorescence in ATC tissues and cell line 8505c. Luciferase reporter assay was performed to examine the effect of wild-type p53 on NIS. Radioiodide uptake assay and flow cytometry analysis were used to detect the role of wild-type p53 on radioiodide uptake.and cell apoptosis in ATC cell line. Results: We showed that the p53 mutation can be detected in ATC tissues. Furthermore, we demonstrated that wild-type p53 transactivated the NIS promoter. In 8505c cells transfected with wild-type p53, treatment with radioiodine resulted in increased radioiodine uptake and increased apoptotic cell death compared with 8505c cells harboring the p53 mutation. Conclusion: In summary, transfection with wild-type p53 can increase the therapeutic effect of radioiodine by regulating the expression of the NIS.

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“…Thyroid cancer is also the seventh most common type of cancer in Canadians, and there were ~5,650 cases of thyroid cancer diagnosed in 2012 (1,2). Concurrently, equal trends in the increase in incidence rate have been identified all over the world (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The age-standardized incidence rate of thyroid cancer has increased from 1.1/100,000 to 6.1/100,000 for males, and from 3.3/100,000 to 22.2/100,000 for females, from 1970 to 1972 in the USA (1,15).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effects of adenovirus‑mediated CD and NIS expression combined with Na131I/5‑FC on human thyroid cancer

et al. 2017

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Abstract. Thyroid cancer is the most common type of malignant endocrine tumor diagnosed. Previous studies have indicated that gene therapy is the most promising and effective therapeutic method for thyroid cancer. Therefore, in the present study, Na 131 I/5-fluorocytosine (5-FC) treatment was combined with cytosine deaminase (CD, encoded by the CDA gene) and sodium iodide symporter (NIS, encoded by the SLC5A5 gene) to act together as a therapeutic tool for thyroid cancer. The present study explored the combined cytotoxic effects of adenovirus-mediated CD and NIS under the control of the progression elevated gene-3 (PEG-3) promoter (Ad-PEG-3-CD-NIS) with Na 131 I/5-FC against the human thyroid cancer TT cell line in vitro. The PEG-3 fragment was obtained by polymerase chain reaction (PCR) using rat genomic DNA as the template, and then Ad-PEG-3-CDA-SLC5A5 was constructed using XbaI. TT cells were transfected by recombinant adenovirus. The method of reverse transcription-quantitative PCR was performed to test the expression of CD and NIS at the level of transcription. The morphological change was assessed by fluorescence microscopy and investigated by western blot analysis. An MTT assay was used to determine the number of living cells inhibited by single or combination therapies on TT cells. The results indicated that the PEG-3 was successfully cloned, and was also positively regulated in 293 cells. CDA and SLC5A5 genes were highly expressed in TT cells. Na 131 I combined with 5-FC significantly decreased the human thyroid cancer cells. In conclusion, combination therapy of Ad-PEG3-CDA-SLC5A5 and Na 131 I/5-FC induces significantly more apoptotic characteristics than either single treatment with Ad-PEG-3-CDA-SLC5A5 or Na 131 I/5-FC, and low doses of Ad-PEG-3-CDA-SLC5A5 enhanced the cytotoxic effects.

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

Cited by 19 publications

References 59 publications

Cholangiocarcinoma: from molecular biology to treatment

Cholangiocarcinoma: from molecular biology to treatment

Wild-Type P53 Induces Sodium/Iodide Symporter Expression Allowing Radioiodide Therapy in Anaplastic Thyroid Cancer

Therapeutic effects of adenovirus‑mediated CD and NIS expression combined with Na131I/5‑FC on human thyroid cancer

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