Autoregulation of thyroid-specific gene transcription by thyroglobulin

Suzuki, Koichi; Lavaroni, Stefano; Mori, Atsumi; Ohta, Masanori; Saito, Jun; Pietrarelli, Michele; Singer, Dinah S.; Kimura, Shioko; Katoh, Ryohei; Kawaoi, Akira; Kohn, Leonard D.

doi:10.1073/pnas.95.14.8251

Cited by 132 publications

(188 citation statements)

References 46 publications

(89 reference statements)

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“…This heterogeneous expression of TTF-1 mRNA among normal thyroid follicles may indicate the presence of an autoregulation mechanism for thyroid-specific gene transcription. Recently, we hypothesized that TG-initiated, transcriptional regulation of thyroid-restricted genes is a normal, feedback, compensatory mechanism that limits follicular function and contributes to follicular heterogeneity (20).…”

Section: Discussionmentioning

confidence: 99%

Thyroid Transcription Factor-1 in Normal, Hyperplastic, and Neoplastic Follicular Thyroid Cells Examined by Immunohistochemistry and Nonradioactive In Situ Hybridization

et al. 2000

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Thyroid transcription factor-1 (TTF-1) has been known to regulate the transcriptional activity of thyroid-specific genes. We examined the expression of TTF-1 in non-neoplastic and neoplastic thyroid tissues. By immunohistochemistry, the nuclei of normal and hyperplastic follicular cells strongly reacted with the antibody against TTF-1. Immunohistochemistry also revealed a distinctive nuclear positivity of TTF-1 in all 33 differentiated follicular cell tumors, including 15 follicular adenomas, 5 follicular carcinomas, and 13 papillary carcinomas. No immunoreactions were observed in three of four undifferentiated carcinomas, whereas an isolated and weak nuclear positivity was obtained in one. In normal and hyperplastic tissues, the distribution of TTF-1 was fairly related to that of thyroid-specific proteins thyroglobulin and thyroperoxidase. However, discrepancies in the distribution were observed in tumor tissues. By in situ hybridization, the riboprobe hybridized distinctively with the cytoplasm of neoplastic cells as well as normal follicular cells. Papillary carcinoma cells expressed TTF-1 mRNA in all but two cases, and its expression was also demonstrated in one of four undifferentiated carcinomas. Reverse transcription-polymerase chain reaction confirmed the presence of TTF-1 mRNA in two human undifferentiated carcinoma cell lines, TTA-1 and TTA-2. In conclusion, the investigation of TTF-1 provides useful information on the functional activities and/or differentiation of thyroid tumors and may lead to an increase in our understanding of the biologic nature of thyroid tumors.

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Section: Discussionmentioning

confidence: 99%

Thyroid Transcription Factor-1 in Normal, Hyperplastic, and Neoplastic Follicular Thyroid Cells Examined by Immunohistochemistry and Nonradioactive In Situ Hybridization

et al. 2000

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“…No TG or TPO mRNA derived from FRTL-5 cells was detected in the TG negative fraction, which mainly contained 8305C cells. In the FRTL-5 cells, the expression of the TG and TPO genes is controlled in a similar manner; thus, FRTL-5 cells that overexpress TG mRNA also overexpress TPO mRNA (23). In this study, FRTL-5 cells showing a strong fluorescence signal were sorted as the TG mRNA positive fraction.…”

Section: Discussionmentioning

confidence: 95%

Messenger RNA quantification after fluorescence‐activated cell sorting using in situ hybridization

et al. 2010

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Recent studies using stem cells or cancer stem cells have revealed the importance of detecting minor populations of cells in blood or tissue and analyzing their biological characteristics. The only possible method for carrying out such procedures is fluorescence-activated cell sorting (FACS). However, FACS has the following two limitations. First, cells without an appropriate cell surface marker cannot be sorted. Second, some laborious procedures such as rapid sorting or treatment under sterilized conditions may require in order to analyze their biological characteristics. If a specific mRNA in a particular cell type can be stained with a florescent dye and then the cells can be sorted without causing RNA degradation, a more simple and universal method for sorting and analyzing cells with a specific gene expression pattern could be established since the biological characteristics of the sorted cells could then be determined by analyzing their gene expression profile. In this study, we established a basic protocol for messenger RNA quantification after FACS (FACS-mQ) using a cRNA probe. This method could be used for the detection and analysis of stem cells or cancer stem cells in various tissues. '

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“…Suzuki et al (79) have shown that thyroglobulin (TG) accumulated in the follicular lumen is a potent suppressor of NIS mRNA levels, in addition to decreasing mRNA levels of TG itself, TPO, and TSH receptor (TSHR). Follicular TG seems to decrease TG, TPO and NIS expression secondary to a decrease in Pax-8 mRNA and protein levels.…”

Section: Other Factorsmentioning

confidence: 99%

The importance of sodium/iodide symporter (NIS) for thyroid cancer management

Carvalho

Ferreira

2007

Arq Bras Endocrinol Metab

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The thyroid gland has the ability to uptake and concentrate iodide, which is a fundamental step in thyroid hormone biosynthesis. Radioiodine has been used as a diagnostic and therapeutic tool for several years. However, the studies related to the mechanisms of iodide transport were only possible after the cloning of the gene that encodes the sodium/iodide symporter (NIS). The studies about the regulation of NIS expression and the possibility of gene therapy with the aim of transferring NIS gene to cells that normally do not express the symporter have also become possible. In the majority of hypofunctioning thyroid nodules, both benign and malignant, NIS gene expression is maintained, but NIS protein is retained in the intracellular compartment. The expression of NIS in non-thyroid tumoral cells in vivo has been possible through the transfer of NIS gene under the control of tissue-specific promoters. Apart from its therapeutic use, NIS has also been used for the localization of metastases by scintigraphy or PET-scan with 124 I. In conclusion, NIS gene cloning led to an important development in the field of thyroid pathophysiology, and has also been fundamental to extend the use of radioiodine for the management of non-thyroid tumors. A glândula tireóide tem capacidade de captar e concentrar iodeto, etapa fundamental na biossíntese dos hormônios tireóideos. O uso de iodo radioativo para fins de diagnóstico e terapia das doenças da tireóide vem sendo feito há muitos anos. Entretanto, somente após a clonagem do gene que codifica o cotransportador de sódio/iodeto (NIS) houve aumento significativo dos estudos relacionados ao mecanismo de transporte de iodeto. Os estudos sobre a regulação da expressão do NIS e a possibilidade de terapia gênica visando à transferência do gene NIS para células que normalmente não expressam esse transportador, foram também viabilizados. Na maior parte dos nódulos tireóideos hipofuncionantes, tanto benignos quanto malignos, a expressão do gene do NIS está presente, mas a proteína NIS fica retida no compartimento intracelular. A transferência do gene usando-se promotores tecido-específicos possibilitou a expressão do NIS em células tumorais não-tireóideas in vivo. Além do seu uso terapêutico, o NIS também vem sendo usado para a localização de metástases tumorais através da cintilografia ou do PET-scan usando-se 124 I. Em conclusão, a clonagem do NIS possibilitou enorme avanço na área de fisiopatologia tireóidea e foi também fundamental para estender o uso do radioiodo para tumores não tireóideos.

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Autoregulation of thyroid-specific gene transcription by thyroglobulin

Cited by 132 publications

References 46 publications

Thyroid Transcription Factor-1 in Normal, Hyperplastic, and Neoplastic Follicular Thyroid Cells Examined by Immunohistochemistry and Nonradioactive In Situ Hybridization

Thyroid Transcription Factor-1 in Normal, Hyperplastic, and Neoplastic Follicular Thyroid Cells Examined by Immunohistochemistry and Nonradioactive In Situ Hybridization

Messenger RNA quantification after fluorescence‐activated cell sorting using in situ hybridization

The importance of sodium/iodide symporter (NIS) for thyroid cancer management

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