scholarly journals Overexpression of the alpha-thyroid hormone receptor in avian cell lines. Effects on expression of the malic enzyme gene are selective and cell-specific.

1992 ◽  
Vol 267 (17) ◽  
pp. 12299-12306
Author(s):  
F.B. Hillgartner ◽  
W Chen ◽  
A.G. Goodridge
Keyword(s):  
Thyroid Hormone ◽  
Cell Lines ◽  
Hormone Receptor ◽  
Malic Enzyme ◽  
Thyroid Hormone Receptor ◽  
Enzyme Gene ◽  
Avian Cell ◽  
Malic Enzyme Gene

scholarly journals Thyroid hormone receptor β mutations in the ‘hot-spot region’ are rare events in thyroid carcinomas

2007 ◽  
Vol 192 (1) ◽  
pp. 83-86 ◽  
Author(s):  
Ana Sofia Rocha ◽  
Ricardo Marques ◽  
Inês Bento ◽  
Ricardo Soares ◽  
João Magalhães ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Hormone ◽  
Transgenic Mice ◽  
Cell Lines ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hot Spot ◽  
Direct Sequencing ◽  
Human Thyroid ◽  
Thyroid Hormone Receptor Β

Thyroid cancer constitutes the most frequent endocrine neoplasia. Targeted expression of rearranged during transfection (RET)/papillary thyroid carcinoma (PTC) and V600E V-raf murine sarcoma viral oncogene homolog B1 (BRAF) to the thyroid glands of transgenic mice results in tumours similar to those of human PTC, providing evidence for the involvement of these oncogenes in PTC. Kato et al. developed a mouse model that mimics the full spectrum of the human follicular form of thyroid cancer (FTC). FTC rapidly develops in these mice through introduction of the thyroid hormone receptor β (THRB)PV mutant on the background of the inactivated THRB wt locus. Our aim was to verify if, in the context of human follicular thyroid carcinogenesis, THRB acted as a tumour suppressor gene. We screened for mutations of the THRB gene in the hot-spot region, spanning exons 7–10, in 51 thyroid tumours and six thyroid cancer cell lines by PCR and direct sequencing. We did not find mutations in any of the tumours or cell lines analysed. Our findings suggest that, in contrast to the findings on the THRB-mutant transgenic mice, THRB gene mutations are not a relevant mechanism for human thyroid carcinogenesis.

scholarly journals The Effect of Thyroid Hormone on the Chromatin Structure and Expression of the Malic Enzyme Gene in Hepatocytes

1988 ◽  
Vol 2 (7) ◽  
pp. 619-626 ◽  
Author(s):  
Stephen J. Usala ◽  
W. Scott Young ◽  
Hajimu Morioka ◽  
Vera M. Nikodem
Keyword(s):  
Thyroid Hormone ◽  
Chromatin Structure ◽  
Malic Enzyme ◽  
Enzyme Gene ◽  
Malic Enzyme Gene

scholarly journals Hexachlorobenzene, a Dioxin-Type Compound, Increases Malic Enzyme Gene Transcription through a Mechanism Involving the Thyroid Hormone Response Element1

Endocrinology ◽  
1999 ◽  
Vol 140 (9) ◽  
pp. 4142-4151 ◽  
Author(s):  
Andrea I. Loaiza-Pérez ◽  
Maria-Teresa Seisdedos ◽  
Diana L. Kleiman de Pisarev ◽  
Horacio A. Sancovich ◽  
Andrea S. Randi ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Gene Transcription ◽  
Malic Enzyme ◽  
Hormone Response ◽  
Enzyme Gene ◽  
Type Compound ◽  
Malic Enzyme Gene

scholarly journals Overexpression of thyroid hormone receptor beta1 is associated with thyrotropin receptor gene expression and proliferation in a human thyroid carcinoma cell line

2000 ◽  
Vol 165 (2) ◽  
pp. 379-389 ◽  
Author(s):  
ST Chen ◽  
HY Shieh ◽  
JD Lin ◽  
KS Chang ◽  
KH Lin
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Thyroid Hormone ◽  
Cell Line ◽  
Cell Lines ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Human Thyroid ◽  
Thyrotropin Receptor ◽  
Tshr Gene

To correlate the differentiation phenotype of two human thyroid cancer cell lines with their expression of various molecular markers, we analyzed the mRNA levels of four thyroid-specific genes, including thyrotropin receptor (TSHR), thyroglobulin (Tg), thyroid transcription factor-1 (TTF-1), and paired-box containing transcription factor-8 (PAX-8) genes. The results showed a differentiation-status-related pattern in which a well-differentiated cell line (WRO) expressed all the four genes, in contrast to an anaplastic cell line (ARO) that expressed TTF-1 and reduced levels of TSHR, but no Tg or PAX-8 genes. Furthermore, to verify the finding of concomitant loss of beta subtype thyroid hormone receptor (TRbeta) and TSHR gene expression in neoplastic thyroid tumors (Bronnegard et al. 1994), we examined the expression levels of TRbeta1 gene in these cell lines. Whereas the WRO cells produced an abundant amount of TRbeta1 protein detectable by immunoprecipitation, the ARO cells produced none. This new observation prompted us to investigate whether overexpression of TRbeta1 protein in ARO cells might produce changes in the differentiation phenotypes. We found that the level of expression of the TSHR gene and the proliferative index of ARO cells were significantly upregulated in the cells stably transfected with wild-type TRbeta1. These findings suggest that TRbeta1 protein overexpression can affect the differentiation phenotypes and induce more efficient cell proliferation of the anaplastic ARO cells.

scholarly journals Thyroid Hormone Receptor β (THRB) Is a Major Target Gene for MicroRNAs Deregulated in Papillary Thyroid Carcinoma (PTC)

2011 ◽  
Vol 96 (3) ◽  
pp. E546-E553 ◽  
Author(s):  
Krystian Jazdzewski ◽  
Joanna Boguslawska ◽  
Jaroslaw Jendrzejewski ◽  
Sandya Liyanarachchi ◽  
Janusz Pachucki ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Hormone Receptor ◽  
Untranslated Region ◽  
Normal Tissue ◽  
Thyroid Hormone Receptor ◽  
Papillary Thyroid ◽  
Down Regulation

Context: Loss of the thyroid hormone receptor is common in tumors. In mouse models, a truncated THRB gene leads to thyroid cancer. Previously, we observed up-regulation of the expression of eight microRNAs (miRs) in papillary thyroid carcinoma (PTC) tumors. Objective: Our objective was to determine whether THRB might be inhibited by miRs up-regulated in PTC. Design: The potential binding of miR to the 3′-untranslated region of THRB was analyzed in silico. Direct inhibition by miRs binding to the cloned 3′-untranslated region of THRB was evaluated using luciferase assays. Inhibition of endogenous THRB and its target genes (DIO1 and APP) was examined in cell lines transfected by pre-miRs. The impact on thyroid hormone response element (TRE) was evaluated in promoter assays. Correlations between the expression of THRB and miRs was evaluated in 13 PTC tumor/normal tissue pairs. Results: THRB contains binding sites for the top seven miRs up-regulated in PTC (P = 0.0000002). Direct interaction with THRB was shown for miR-21 and miR-146a. We observed lower levels of THRB transcripts in cell lines transfected with miR-21, -146a, and -221 (down-regulation of 37–48%; P < 0.0001), but not with miR-181a. THRB protein was suppressed down to 10–28% by each of four miRs. Concomitant expression of DIO1 and APP was affected (down-regulation of 32–66%, P < 0.0034 and up-regulation of 48–57%, P < 0.0002, respectively). All four miRs affected TRE activity in promoter assays. Down-regulation of luciferase occurred after transfection with pTRE-TK-Luc construct and each of four miRs. The analysis of tumor/normal tissue pairs revealed down-regulation of THRB in 11 of 13 pairs (1.3- to 9.1-fold), and up-regulation of miR-21, -146a, -181a, and -221 in almost all pairs. Conclusions: MiRs up-regulated in PTC tumors directly inhibit the expression of THRB, an important tumor suppressor gene.

scholarly journals Thyroid hormone receptor beta inhibits the PI3K-Akt-mTOR signaling axis in anaplastic thyroid cancer cell lines via genomic mechanisms

2021 ◽  
Author(s):  
Cole D Davidson ◽  
Eric L Bolf ◽  
Noelle E Gillis ◽  
Lauren M Cozzens ◽  
Jennifer A Tomczak ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Hormone ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Anaplastic Thyroid Cancer ◽  
Regulatory Subunit ◽  
Pi3k Signaling ◽  
Receptor Beta

Abstract Thyroid cancer is the most common endocrine malignancy, and the global incidence has increased rapidly over the past few decades. Anaplastic thyroid cancer (ATC) is highly aggressive, dedifferentiated, and patients have a median survival of fewer than six months. Oncogenic alterations in ATC include aberrant PI3K signaling through receptor tyrosine kinase (RTK) amplification, loss of phosphoinositide phosphatase expression and function, and Akt amplification. Furthermore, the loss of expression of the tumor suppressor thyroid hormone receptor beta (TRβ) is strongly associated with ATC. TRβ is known to suppress PI3K in follicular thyroid cancer and breast cancer by binding to the PI3K regulatory subunit p85⍺. However, the role of TRβ in suppressing PI3K signaling in ATC is not completely delineated. Here we report that TRβ indeed suppresses PI3K signaling in ATC cell lines through unreported genomic mechanisms including a decrease in RTK expression and increase in phosphoinositide and Akt phosphatase expression. Furthermore, the reintroduction and activation of TRβ in ATC cell lines enables an increase in the efficacy of the competitive PI3K inhibitors LY294002 and buparlisib on cell viability, migration, and suppression of PI3K signaling. These findings not only uncover additional tumor suppressor mechanisms of TRβ but shed light into the implication of TRβ status and activation on inhibitor efficacy in ATC tumors.

Sign in / Sign up

Export Citation Format

Share Document