| Identification of naturally occurring dominant negative mutants of thyroid hormone alpha 1 and beta 1 receptors in a human hepatocellular carcinoma cell line. | |
| | |
MedLine Citation:
|
PMID: 8828459 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
To understand the function of thyroid hormone nuclear receptors (TRs) in human hepatocellular carcinoma cells (HCC), we characterized the hormone binding and transactivational activity of TRs in a HCC cell line, J7. TR alpha 1 (J7-TR alpha 1) and TR beta 1 (J7-TR beta 1) complementary DNAs were cloned from this cell line, and the binding activity to the hormone response elements (TREs) and to the thyroid hormone, 3,3',5-triiodo-L-thyronine (T3) of the expressed TR proteins were evaluated. J7-TR alpha 1 and J7-TR beta 1 bound to TREs similarly as the TRs isolated from other tissues. However, J7-TR alpha 1 did not bind to T3, and J7-TR beta 1 bound to T3 with only about 10% the affinity of the wild-type TR beta 1. Sequencing of the complementary DNAs shows a single Met259Ile mutation in J7-TR alpha 1 and Met334Val in J7-TR beta 1. Using reporters containing TREs, we found that J7-TR alpha 1 and J7-TR beta 1 had virtually lost their transactivational activity. Moreover, these two mutants inhibited the transactivational activity of the wild-type TRs by a dominant negative effect not only on the transfected TRs, but also on endogenous TRs in other two HCC cell lines, SK-Hep-1 and HepG2. The potency of the dominant negative effect of these two mutants inversely correlated with the expression level of endogenous TRs. The present studies identified two novel naturally occurring TR mutants that have potent dominant negative action. The identification of both the alpha and beta dominant negative mutants in J7 made this cell line a useful model system to further understand the molecular mechanism of the dominant negative action of TR mutants. |
| | |
Authors:
|
K H Lin; X G Zhu; H Y Shieh; H C Hsu; S T Chen; P McPhie; S Y Cheng |
Related Documents
:
|
6808059 - Comparative assays in three laboratories of serum specimens containing pregnancy-specif... 17927449 - Putting beta-diversity on the map: broad-scale congruence and coincidence in the extremes. 11980879 - Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer ... 3708909 - A mouse monoclonal ige antibody anti bovine milk beta-lactoglobulin allows studies of a... 9276819 - Effects of milk protein genotypes on the variation for milk production traits of holste... 2809279 - High levels of circulating neutralizing antibody in normal animals to recombinant mouse... 17560549 - Resveratrol abolishes resistance to axonal degeneration in slow wallerian degeneration ... 16828089 - Reduced pde4 expression and activity contributes to enhanced catecholamine-induced camp... 18813789 - Glioma gene therapy with soluble transforming growth factor-beta receptors ii and iii. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Endocrinology Volume: 137 ISSN: 0013-7227 ISO Abbreviation: Endocrinology Publication Date: 1996 Oct |
Date Detail:
|
Created Date: 1996-12-18 Completed Date: 1996-12-18 Revised Date: 2008-11-21 |
Medline Journal Info:
|
Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 4073-81 Citation Subset: AIM; IM |
Affiliation:
|
Department of Biochemistry, Chang-Guang College of Medicine and Technology, Taoyuan, Taiwan, Republic of China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Carcinoma, Hepatocellular
/
metabolism*,
pathology DNA / genetics Genes, Dominant* Humans Liver Neoplasms / metabolism*, pathology Point Mutation* Promoter Regions, Genetic Receptors, Thyroid Hormone / genetics*, metabolism* Transcriptional Activation Triiodothyronine / metabolism Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
|
0/Receptors, Thyroid Hormone; 6893-02-3/Triiodothyronine; 9007-49-2/DNA |
| Comments/Corrections | |
Comment In:
|
Endocrinology. 1996 Oct;137(10):4071-2
[PMID:
8828458
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Role of BRCA1 mutation screening in the management of familial ovarian cancer.
Next Document: Amino acid substitutions of thyroid hormone receptor-beta at codon 435 with resistance to thyroid ho...