Characterization of a thyroid hormone receptor expressed in human kidney and other tissues.

Nakai, Asami; Seino, Susumu; Sakurai, Akihiro; Szilak, Illya; Bell, Graeme I.; DeGroot, Leslie J.

doi:10.1073/pnas.85.8.2781

Cited by 117 publications

(48 citation statements)

References 23 publications

(21 reference statements)

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“…The remainder matched to the following sequences: cadherin-6, caldesmon, laminin, glutamin synthetase, tropomyosin, c-erb A-α2, cyclin B, lactate dehydrogenase B, cyclin B2, and PTI-1. The 130 bp cDNA fragment (designated T 11 CAP 2 NPCl-8), identified in all three NPC cell lines ( Figure 1A), showed 98% homology with the 3′-untranslated region of human TR-α2 (c-erb A-α2) (Nakai et al, 1988) (Figure 1B). When utilized as a probe, a 2.7 kb transcript was detected in all three NPC cell lines (Figure 2A, lanes 1-3) but not in normal control obtained from a randomly-picked individual (Figure 2A, lane 4) or pooled samples (Figure 2A, lane 5).…”

Section: Resultsmentioning

confidence: 99%

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Elevated expression of thyroid hormone receptor α 2 (c-erb A-α2) in nasopharyngeal carcinoma*

et al. 2000

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Nasopharyngeal carcinoma (NPC) is an endemic cancer with a very high incidence in South China and Southeast Asia such as Hong-Kong and Taiwan. Epstein-Barr virus (EBV), genetic factors (human HLA type A2-BW42 and cytochrome p4502E1-CYP2E1), and certain dietary (nitrosamine, herbal medicine) and environmental conditions (smoking, occupational exposures) have been shown to be involved in the development of NPC (Hildesheim and Levine, 1993), but the molecular mechanisms by which NPC was generated remained largely unknown. Overexpression of Myc oncogene was detected in NPC cell lines (Lin et al, 1993) and in some NPC tumours (Porter et al, 1994). Bcl-2 was up-regulated and was detected in most samples of NPC (Lu et al, 1993). Mutations in p53 tumour suppressor gene (Spruck et al, 1992) and RB/p105 gene (Sun et al, 1993) in NPC are relatively rare. Lately, mutations in the RB2/p130 gene were detected in 30% of primary human NPCs (Claudio et al, 2000). Though decreased level of expression was reported, no point mutation of the potential tumour suppressor gene p16 was detected in NPC (Sun et al, 1995). These studies suggested the importance of other genes in NPC oncogenesis.Various tools such as cytogenetic analysis (Mitelman et al, 1983;Huang et al, 1989), loss of heterozygosity (LOH) (Huang et al, 1991;Hu et al, 1996;Mutirangura et al, 1997), and comparative genomic hybridization (CGH) Hui et al, 1999) have been employed to investigate the candidate genes associated with NPC. These studies offered a genome-wide investigation based upon a comprehensive pattern of DNA sequence copy number changes. Alterations due to mutations and/or regulation dysfunction can hardly be detected. Differential display (DD) (Fung et al, 1998) and cDNA representational difference analysis (RDA) (Zhan et al, 1998) offered alternative screening tools. We had adopted differential display for the study of differences in gene-expression patterns between normal nasal epithelial and transformed nasopharyngeal epithelial cells. The elevated expression of TR-α2 in NPC cell lines was demonstrated. RNA in situ hybridization of TR-α2 transcripts among biopsies derived from NPC cases and control subjects was employed to substantiate the in vitro finding. MATERIALS AND METHODS Cell cultureBiopsied tissues of nasal polyps and turbinates were collected from National Taiwan University Hospital and Mackay Memorial Hospital, Taipei. After removal of blood clots with three washes of sterile phosphate buffered saline (PBS), these samples were added into Dulbecco's minimum essential medium (DMEM) supplemented with 0.1 mM nonessential amino acids, 50 U ml -1 penicillin, 50 µg ml -1 streptomycin, 1.25 µg ml -1 fungizone and 1 mg ml -1 pronase. After an overnight incubation at 4˚C, carcass was discarded and the suspension was centrifuged at 1,500 rpm for 10 min at room temperature. The pelleted cells were resuspended in DMEM supplemented with 10% fetal bovine serum, 0.1 mM nonessential amino acids, 50 U ml -1 penicillin, 50 µg ml -1 streptomycin, 1.25 µg ml -1 fu...

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Section: Resultsmentioning

confidence: 99%

“…Southern blot analysis was Sequences of primers employed to generate the cDNA fragment are underlined. The numbering of c-erb A-α2 sequences is based upon that reported by Nakai et al (1988) performed to investigate the genomic organization of TR-α gene in NPC cell lines. No amplification or obvious DNA rearrangement was observed (Figure 3).…”

Section: Resultsmentioning

confidence: 99%

Elevated expression of thyroid hormone receptor α 2 (c-erb A-α2) in nasopharyngeal carcinoma*

et al. 2000

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“…c-erb-A a was originally described in rat brain (9), and has been termed the a1 form following the discovery of c-erb-A a2 in human testis (10) and kidney (1 1). c-erb-A a2 mRNA is the most widely distributed, and appears to be present at low concentration in most tissues (10,11). However, the importance and significance of type a2 has been questioned consequent to recent discordant reports on T, binding.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, this internal Eco RI site, characteristic of the c-erb-A a2 form (I I), is close (120 bp) to the 3' end of the amino-acid sequence coded for by this cDNA, and is therefore downstream of the putative thyroid hormone binding domain. Since clone 29 extends 381 bp further upstream than clone 32, clone 32 is therefore, presumably, a truntated version of clone 29, and comparisons with other sequences (see below) are shown only for clone 29. A comparative analysis of the DNA and T,/T, ligand binding domains in rat c-erb-A a1 (9) and human c-erb-A a2 (10,11,19) with the corresponding region of clone 29 showed a high degree of nucleotide homology (> 900/) (Fig. 1).…”

Section: Isolation and Nucleotide Sequence Of Neuroblastoma C-erb-a Cmentioning

confidence: 99%

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Molecular Cloning and Characterization of c‐erb‐A mRNA Species in Mouse Neuroblastoma Cells

Moeller

Rapoport

Gavin

1989

J Neuroendocrinology

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The mouse neuroblastoma cell line is an excellent model in which to study thyroid hormone action and metabolism, particularly in neural tissue. We therefore undertook the molecular cloning and characterization in these cells of putative thyroid hormone receptors related to c-erb-A. Since rat brain tissue contains multiple cell types, and because of possible subtle differences between species (mouse and rat), we therefore screened a new cDNA library constructed from mouse neuroblastoma cell mRNA with synthetic oligonucleotide probes based on the published nucleotide sequence of the c-erb-A gene in whole rat brain. Despite the fact that this rat brain cDNA sequence is now recognized to represent a c-erb-A a1 form, the cDNA clones that we isolated were all members of the newly-recognized c-erb-A a2 form. This identification was made on the basis of nucleotide sequence divergence downstream of the nucleotide corresponding to amino-acid residue 370 in the predicted coding region. The two longest mouse neuroblastoma cDNA clones, clone 29 (1796 bp) and clone 32 (1410 bp), were 93% to 94% homologous with the c-erb-A ct2 and c-erb-A a1 forms in their DNA binding and thyroid hormone binding domains (up to amino-acid residue 370 in the latter). Both clones 29 and 32 were incomplete in that they terminated at their 3' ends at an internal Eco R1 site. Fortunately this 120 bp (40 derived amino-acid) truncation was downstream of the reported thyroid hormone binding domain. The 5' untranslated end of clone 29 (446 bp) was of interest because a region of its nucleotide sequence (279 bp) revealed a high degree of homology (87%) with rat brain c-erb-A a l . This highly conserved region in clone 29 appeared to be important in the regulation of translation because only clone 32, in which this region was truncated, efficiently translated protein in a cell-free system. The protein product of clone 32 did not bind thyroid hormone. Northern blot analysis of mouse neuroblastoma mRNA with site-specific synthetic oligonucleotides revealed that the c-erb-A cr2 species was dominant (major band of 2.4 kb), with a lesser amount of the c-erb-A a1 species (major band of 1.8 kb).In conclusion: 1) We report the molecular cloning of c-erb-A variants in a specific neural tissue cell type, namely mouse neuroblastoma cells; 2) The cells contained predominantly the c-erb-A a2 subtype; 3) This c-erb-A a2 form was unique up to bp 167 at its 5 untranslated end, and was then followed, up to the ATG initiation codon, by a highly conserved region common to all c-erb-A a species; 4) The 5' untranslated region appeared to play a role in the translational efficiency of this mRNA; 5) The protein product of the c-erb-A a2 mRNA in these cells did not appear to bind thyroid hormone. In view of this finding, the physiological role of the c-erb-A a2 protein remained speculative and may involve a repressor function at the thyroid hormone responsive element.

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New point mutation (R243W) in the hormone binding domain of the c-erbA β1 gene in a family with generalized resistance to thyroid hormone

et al. 1996

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Characterization of a thyroid hormone receptor expressed in human kidney and other tissues.

Cited by 117 publications

References 23 publications

Elevated expression of thyroid hormone receptor α 2 (c-erb A-α2) in nasopharyngeal carcinoma*

Elevated expression of thyroid hormone receptor α 2 (c-erb A-α2) in nasopharyngeal carcinoma*

Molecular Cloning and Characterization of c‐erb‐A mRNA Species in Mouse Neuroblastoma Cells

New point mutation (R243W) in the hormone binding domain of the c-erbA β1 gene in a family with generalized resistance to thyroid hormone

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