Growth Regulation of Normal Thyroids and Thyroid Tumors in Man

Goretzki, P. E.; Frilling, A.; Simon, Dietmar; Roeher, H. D.

doi:10.1007/978-3-642-83816-3_6

Cited by 123 publications

(86 citation statements)

References 30 publications

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“…3A) respectively and were derived from follicular, papillary and anaplastic thyroid tumours respectively (20,22,23). The overall activity patterns of transfected constructs were comparable in the three cell lines (Fig.…”

Section: Resultsmentioning

confidence: 90%

Molecular cloning of a functional promoter of the human plakoglobin gene

Pötter

Braun

Lehmann³

et al. 2001

European Journal of Endocrinology

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Objective: Plakoglobin (Pg) is the only cytoplasmic protein component common to both junctional complexes mediating cell±cell adhesion, adherens junctions and desmosomes. In these complexes Pg appears to act as a linker protein anchoring transmembrane proteins of the cadherin superfamily to the actin cytoskeleton and intermediate ®lament system respectively. Intercellular adhesion is frequently disturbed in skin diseases and in carcinomas, enabling tumour progression and metastasis. Whereas Pg expression is lost in some thyroid tumours and carcinoma cell lines, little information on Pg gene regulation is currently available owing to a lack of promoter studies. Design and methods: We have cloned and sequenced genomic DNA from a human library that resulted in 979 bp upstream of the published Pg cDNA. The transcriptional start was mapped by rapid ampli®cation of cDNA ends. Methylation-speci®c PCR of bisul®te-modi®ed cell line DNA was applied to probe the methylation status of a promoter-associated CpG island. Reporter-gene constructs of various promoter fragments were transiently transfected in thyroid carcinoma cell lines and their activities were determined by luciferase measurements. Results and conclusions: A 1 kb DNA fragment harbouring a functional promoter of the human Pg gene was cloned and characterized. The sequence lacks a canonical TATA box, but contains putative CCAAT boxes as well as various putative binding sites for transcription factors, among them SP1 and AP2, proximal to the transcriptional start. Considerable promoter activity was found in thyroid cell lines and deletion analysis indicated that a 300 bp region proximal to the 5 H -untranslated region of the mRNA represents the minimal promoter of the human Pg gene. As cells lacking endogenous Pg expression were found to contain methylated CpG dinucleotides in a CpG island located around the transcriptional start site, it is suggested that epigenetic mechanisms such as DNA methylation contribute to dysregulated Pg expression.

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Section: Resultsmentioning

confidence: 90%

Molecular cloning of a functional promoter of the human plakoglobin gene

Pötter

Braun

Lehmann³

et al. 2001

European Journal of Endocrinology

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“…To investigate the role of RXR agonist in these patients, we took advantage of the RA-resistant thyroid cancer cell line, FTC238, derived from the metastasis of the patient whose cells, at diagnosis, allowed the establishment of the RAsensitive FTC133 cell line (22). In this study, we show that ligands of RARs or RXRs exert different effects in thyroid cancer cells through either differentiation or inhibition of growth and invasion and may thus provide different therapeutic approaches in DTC patients.…”

Section: ) Nis Andmentioning

confidence: 91%

Bexarotene via CBP/p300 Induces Suppression of NF-κB–Dependent Cell Growth and Invasion in Thyroid Cancer

Cras

Politis

Balitrand

et al. 2012

Clinical Cancer Research

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Purpose: Retinoic acid (RA) treatment has been used for redifferentiation of metastatic thyroid cancer with loss of radioiodine uptake. The aim of this study was to improve the understanding of RA resistance and investigate the role of bexarotene in thyroid cancer cells.Experimental Design: A model of thyroid cancer cell lines with differential response to RA was used to evaluate the biological effects of retinoid and rexinoid and to correlate this with RA receptor levels. Subsequently, thyroid cancer patients were treated with 13-cis RA and bexarotene and response evaluated on radioiodine uptake reinduction on posttherapy scan and conventional imaging.Results: In thyroid cancer patients, 13-cis RA resistance can be bypassed in some tumors by bexarotene. A decreased tumor growth without differentiation was observed confirming our in vitro data. Indeed, we show that ligands of RARs or RXRs exert different effects in thyroid cancer cell lines through either differentiation or inhibition of cell growth and invasion. These effects are associated with restoration of RARb and RXRg levels and downregulation of NF-kB targets genes. We show that bexarotene inhibits the transactivation potential of NF-kB in an RXR-dependent manner through decreased promoter permissiveness without interfering with NF-kB nuclear translocation and binding to its responsive elements. Inhibition of transcription results from the release of p300 coactivator from NF-kB target gene promoters and subsequent histone deacetylation.Conclusion: This study highlights dual mechanisms by which retinoids and rexinoids may target cell tumorigenicity, not only via RARs and RXRs, as expected, but also via NF-kB pathway. Clin Cancer Res; 18(2); 442-53. Ó2011 AACR.

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“…The human thyroid carcinoma cell line FTC133 was kindly provided by Professor M. Derwahl, Humboldt University, Germany. The FTC133 cell line was derived from the primary tumor of a 42-year-old male patient with metastatic thyroid follicular carcinoma (24), and then cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum and penicillin/streptomycin in a humidified incubator at 37˚C and 5% CO 2 . Western blot analysis.…”

Section: Methodsmentioning

confidence: 99%

Epithelial-mesenchymal transition triggers cancer stem cell generation in human thyroid cancer cells

Lan

Luo

Cui

et al. 2013

International Journal of Oncology

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Abstract.Increasing evidence has shown that cancer stem cells or tumor initiating cells are the 'root cause' of malignant cancers. However, the exact origin of cancer stem cells still remains obscure in thyroid research. EMT has been implicated in the initiation and conversion of early-stage tumors into invasive malignancies and is associated with the stemness of cancer cells. Based on these facts, a new hypothesis was suggested that EMT induces cancer stem cell generation and tumor progression in human thyroid cancer cells in vitro. In the present study, FTC133 cells identified as EMT-negative cells were used for EMT induction by HIF-1α transfection. Overexpression of HIF-1α induced FTC133 cells to undergo EMT, downregulated the epithelial markers E-cadherin, upregulated the mesenchymal marker vimentin, and associated with highly invasive and metastatic properties. Most importantly, the induction of EMT promoted the stem-like side population cell proportion in the FTC133 cells. These results indicate that EMT induction promotes CSC traits and cell proportions in the thyroid cancer cells, which implies that EMT could induce cancer stem cell generation and tumor progression in thyroid cancers. Further understanding of the role of EMT and cancer stem cells in cancer progression may reveal new targets for the prevention or therapy of thyroid cancers. IntroductionAnaplastic thyroid carcinoma is an aggressive malignancy characterized by an extensive local invasion, early systemic dissemination and marked resistance to chemo-and radiotherapy, and always has a poor prognosis with a mean survival of only few months (1). Current systemic therapy fails to eradicate this cancer or even to stop tumor progress. It has been hypothesized that this may be explained by the failure of current drugs to effectively target cancer stem-like cells (CSCs) (2,3). To date, CSCs have been reported in various solid tumors and in cancer cell lines (4-9). However, until recently, there are only very few studies on adult thyroid stem/progenitor cells and thyroid CSCs (10-12). We and others have recently described and characterized thyroid cancer stem cells as a side population (13-17) that may play a critical role in the progression and recurrence of cancer and its subsequent metastasis (18).Epithelial to mesenchymal transition (EMT) is a vital process for morphogenesis during embryonic development, but it has also been implicated in the conversion of early stage tumors into invasive malignancies (19). More recent studies have further demonstrated that EMT plays a critical role not only in tumor metastasis but also in tumor recurrence that is believed to be tightly linked with the biology of cancer stem-like cells or cancer-initiating cells (20-23). The relationship between EMT and CSCs has been observed, with the evidence suggesting that EMT cells acquire stem cell-like traits and that CSCs exhibit a mesenchymal-like appearance in immortalized non-tumorigenic mammary epithelial cells and breast cancers (22). In thyroid cancer, it was found i...

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Growth Regulation of Normal Thyroids and Thyroid Tumors in Man

Cited by 123 publications

References 30 publications

Molecular cloning of a functional promoter of the human plakoglobin gene

Molecular cloning of a functional promoter of the human plakoglobin gene

Bexarotene via CBP/p300 Induces Suppression of NF-κB–Dependent Cell Growth and Invasion in Thyroid Cancer

Epithelial-mesenchymal transition triggers cancer stem cell generation in human thyroid cancer cells

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