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Lost expression of thyroid hormone receptor-β1 mRNA in esophageal cancer

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Frontiers in Biology 2012年第4期7卷 368-373页

作者： Hao LI Xiao-Chun XU Department of Clinical Cancer Prevention UTM. D. Anderson Cancer Center Houston TX 77030 USA Department of Pathology Anhui Medical University Hefei 230032 China

thyroid hormone receptors （TR）, ligand-mediated transcription factors, regulate cell growth, differentiation, and apoptosis. In humans, two different genes encode TR-α and TR-β and they are often co-expressed in various tissues at different levels. To explore the role of TR in esophageal cancer, we analyzed expression of TR-β1 mRNA （most abundantly expressed in the majority of normal cells） in normal and malignant esophageal tissue specimens using in situ hybridization. The TR-β1 mRNA was detected in 92.3% （96 of 104） of normal esophageal mucosa, whereas TR-β1 mRNA was only detected in 55.8% （58 of 104 cases） of esophageal squamous cell carcinoma specimens （P〈 0.00001）. Expression of TR-β1 mRNA was associated with well-differentiated cancers （P〈 0.001）. Furthermore, we determined whether the loss of heterozygosity （LOH） in TR-β1 gene locus would be responsible for the lost TR-β1 expression. Analysis of 73 esophageal tissue specimens generated 39 informative cases, 17 of which showed LOH （43.6%） but only 9 of these 17 cases were correlated with lost TR-β1 expression. This study demonstrated that expression of TR-β1 mRNA was lost in esophageal cancer tissues, which may be due to multiple mechanisms.

关键词： esophageal cancer thyroid hormone receptor in situ hybridization LOH

Daily exposure to low concentrations Tetrabromobisphenol A interferes with the thyroid hormone pathway in HepG2 cells

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Fundamental Research 2023年第3期3卷 384-391页

作者： Taicheng An Lirong Lu Guiying Li Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health Guangdong Key Laboratory of Environmental Catalysis and Health Risk ControlInstitute of Environmental Health and Pollution ControlGuangdong University of TechnologyGuangzhou 510006China Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control Key Laboratory of City Cluster Environmental Safety and Green Development of the Ministry of EducationSchool of Environmental Science and EngineeringGuangdong University of TechnologyGuangzhou 510006China

Tetrabromobisphenol A(TBBPA)is a flame retardant that adversely affects the environment and human health.The present study exposed HepG2 cells to low concentrations of TBBPA daily to investigate the changes in gene regulation,mainly related to pathways associated with the endocrine system.The quantitative polymerase chain reaction(qPCR)confirmed that prolonged exposure gradually activated the thyroid hormone and parathyroid hormone signaling pathways.The expression levels of genes related to the thyroid hormone signaling pathway were upregulated(1.15-8.54 times)after five generations of exposure to 1 and 81 nM TBBPA.Furthermore,co-exposure to 81 nM TBBPA and 0.5 nM thyroid hormone receptor antagonist for five generations significantly reduced the expression of thyroid hormone and parathyroid hormone receptors.Meanwhile,81 nM TBBPA inhibited the activation of the Ras pathway and downregulated Ras gene expression level(3.7 times),indicating the association between the toxic effect and thyroid hormone receptors.Additionally,our experiments revealed that the thyroid hormone pathway regulated the induction of the Ras signaling pathway by TBBPA.The study thus proves that daily exposure to TBBPA interferes with the thyroid hormone signaling pathway and subsequently the endocrine system.

关键词： TBBPA Low-concentration exposure Endocrine system thyroid hormone receptor Ras signaling pathway

thyroid disruption by technical decabromodiphenyl ether (DE-83R) at low concentrations in Xenopus laevis

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Journal of Environmental Sciences 2010年第5期22卷 744-751页

作者： Xiaofei Qin Xijuan Xia Zhongzhi Yang Shishuai Yan Yaxian Zhao Rongguo Wei Yan Li Mi Tian Xingru Zhao Zhanfen Qin Xiaobai Xu State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-environmental Sciences Chinese Academy of Sciences Beijing 100085 China Chinese Research Academy of Environmental Sciences Beijing 100012 China

Decabromodiphenyl ether （decaBDE）,as a flame retardant,is widely produced and used.To study the thyroid disruption by technical decaBDE at low concentrations,Xenopus laevis tadpoles were exposed to technical decaBDE mixture DE-83R （1-1000 ng/L） in water from stage 46/47 （free swimming larvae,system of Nieuwkoop and Faber） to stage 62.DE-83R at concentration of 1000 ng/L significantly delayed the time to metamorphosis （presented by forelimb emergence,FLE）.Histological examination showed that DE83R at all tested concentrations caused histological alterations-multilayer follicular epithelial cell and markedly increased follicle size accompanied by partial colloid depletion and increase in the peripheral colloid vacuolation,in thyroid glands.All tested concentrations of DE-83R also induced a down-regulation of thyroid receptor mRNA expression.These results demonstrated that technical decaBDE disrupted the thyroid system in X.laevis tadpoles.Analysis of polybrominated diphenyl ethers （PBDEs）（sum of 39 congeners） in X.laevis indicated that mean concentrations of total PBDEs in X.laevis exposed to 1,10,100,1000 ng/L were 11.0,128.1,412.1,1400.2 ng/g wet weight,respectively.Considering that PBDEs burden of X.laevis tadpoles was close to PBDEs levels in amphibians as reported in previous studies,our study has raised new concerns for thyroid disruption in amphibians of technical decaBDE at environmentally relevant concentrations.

关键词： decabromodiphenyl ether Xenopus laevis thyroid disruption metamorphosis thyroid hormone receptor

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thyroid hormone action in metabolic regulation

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Protein & Cell 2011年第5期2卷 358-368页

作者： Yiyun Song Xuan Yao Hao Ying Key Laboratory of Nutrition and Metabolism Institute for Nutritional SciencesShanghai Institutes for Biological SciencesGraduate School of the Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China

thyroid hormone plays pivotal roles in growth,differentiation,development and metabolic homeostasis via thyroid hormone receptors(TRs)by controlling the expression of TR target genes.The transcriptional activity of TRs is modulated by multiple factors including various TR isoforms,diverse thyroid hormone response elements,different heterodimeric partners,coregulators,and the cellular location of TRs.In the present review,we summarize recent advance in understanding the molecular mechanisms of thyroid hormone action obtained from human subject research,thyroid hormone mimetics application,TR isoform-specific knock-in mouse models,and mitochondrion study with highlights in metabolic regulations.Finally,as future perspectives,we share our thoughts about current challenges and possible approaches to promote our knowledge of thyroid hormone action in metabolism.

关键词： thyroid hormone thyroid hormone receptor metabolic regulation central and peripheral effect thyroid diseases

thyroid hormone regulation of apoptotic tissue remodeling during anuran metamorphosis

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Cell Research 2001年第4期11卷 245-252页

作者： SHI YUN-Bo, LIEZHEN FU, SHAO CHUNG VICTOR HSIA, AKIHIRO TOMITA, DANIEL BUCHHOLZ Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Develop- ment, National Institutes of Health, Bethesda, Maryland 20892-5431, USA Laboratory of Gene Regulation and Development National Institute of Child Health and Human Development National Institutes of Health Bethesda USA

Anuran metamorphosis involves systematic transformations of individual organs in a thyroid hormone (TH)-dependent manner. Morphological and cellular studies have shown that the removal of larval or- gans/tissues such the tail and the tadpole intestinal epithelium is through programmed cell death or apop- tosis. Recent molecular investigations suggest that TH regulates metamorphosis by regulating target gene expression through thyroid hormone receptors (TRs), which are DNA-binding transcription factors. Cloning and characterization of TH response genes show that diverse groups of early response genes are induced by TH. The products of these TH response genes are believed to directly or indirectly affect the expression and/or functions of cell death genes, which are conserved at both sequence and function levels in different animal species. A major challenge for future research lies at determining the signaling pathways leading to the activation of apoptotic processes and whether different death genes are involved in the regulation of apoptosis in different tissues/organs to effect tissue-specific transformations.

关键词： Xenopus laevis thyroid hormone receptor extracellular matrix apoptosis.

Distinct expression profiles of transcriptional coactivators for thyroid hormone receptors during Xenopus laevis metamorphosis

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Cell Research 2003年第6期13卷 459-464页

作者： BINDU D PAUL National Institutes of Health Laboratory of Gene Regulation and Development National Institute of Child Health and Human Development Bldg. USA.

The biological effects of thyroid hormone (T3) are mediated by the thyroid hormone receptor (TR). Amphibian metamorphosis is one of the most dramatic processes that are dependent on T3. T3 regulates a series of orchestrated developmental changes, which ultimately result in the conversion of an aquatic herbivorous tadpole to a terrestrial carnivorous frog. T3 is presumed to bind to TRs, which in turn recruit coactivators, leading to gene activation. The best-studied coactivators belong to the p160 or SRC family. Members of this family include SRC1/ NCoA-1, SRC2/TIF2/GRIP1, and SRC3/pCIP/ACTR/AIB-l/RAC-3/TRAM-1. These SRCs interact directly with liganded TR and function as adapter molecules to recruit other coactivators such as p300/CBP. Here, we studied the expression patterns of these coactivators during various stages of development. Amongst the coactivators cloned in Xenopus laevis, SRC3 was found to be dramatically upregulated during natural and T3-induced metamorphosis, and SRC2 and p300 are express

关键词： transcription coactivators thyroid hormone receptor Xenopus laevis metamorphosis histone acetylation.

Amphibian metamorphosis as a model for studying the developmental actions of thyroid hormone

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Cell Research 1998年第4期8卷 259-272页

作者： TATA JAMSHED R (National Institute for Medical Research, The Ridgeway,Mill Hill, London NW7 1AA, UK.Tel: +44-181-959 3666 Fax: +JJ-181-913 8583E-mail: jtata@nimr. mrc. ac. uk) National Institute for Medical Research London U.K.

The thyroid hormones L-thyroxine and triiodo-L-thyronine have profound effects on postembryonic development of most vertebrates. Analysis of their action in mammals is vitiated by the exposure of the developing foetus to a number of maternal factors which do not allow one to specifically define the role of thyroid hormone (TH)or that of other hormones and factors that modulate its action. Amphibian metamorphosis is obligatorily dependent on TH which can initiate all the diverse physiological manifestations of this postembryonic developmental process(morphogenesis, cell death, re-structuring, etc.) in free-living embryos and larvae of most anurans. This article will first describe the salient features of metamorphosis and its control by TH and other hormones. Emphasis will be laid on the key role played by TH receptor (TR), in particular the phenomenon of TR gene autoinduction, in initiating the developmental action of TH. Finally, it will be argued that the findings on the control of amphibian metamorphosis enhance our understanding of the regulation of postembryonic development by TH in other vertebrate species.

关键词： thyroid hormone metamorphosis postembryonic development thyroid hormone receptor autoinduction