Primary structure and expression of a functional human glucocorticoid receptor cDNA

Hollenberg, S M; Weinberger, Cary; Ong, Estelita S.; Cerelli, Gail M.; Oro, Anthony E.; Lebo, Roger V.; Thompson, E. Brad; Rosenfeld, M G; Evans, Ronald M.

doi:10.1038/318635a0

Cited by 1,740 publications

(751 citation statements)

References 63 publications

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“…Excluding occasional sequence alterations introduced by the Taq polymerase, two types of clones could be distinguished ( Figure 1). One of these clones corresponded to the human GR wild-type sequence, 24 differing only in a known silent polymorphism in codon 766 (AAT-AAC), 25 the other differed by a missense mutation in codon 477 (CGC-CAC), leading to an arginine (R)-histidine (H) exchange. To verify the presence of this productive mutation, we amplified genomic DNA encompassing exon 4 and subjected it to bulk sequencing.…”

Section: Resultsmentioning

confidence: 99%

Glucocorticoid receptor heterozygosity combined with lack of receptor auto-induction causes glucocorticoid resistance in Jurkat acute lymphoblastic leukemia cells

et al. 2004

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Glucocorticoids (GC) induce apoptosis in malignant lymphoblasts, but the mechanism of this process as well as that of the clinically important GC resistance is unknown. We investigated GC resistance in Jurkat T-ALL cells in which ectopic GC receptor (GR) restores GC sensitivity, suggesting deficient GR expression. Jurkat cells expressed one wild-type and one mutated (R477H) GR allele. GR R477H ligand-bindingdependent nuclear import, as revealed by live-cell microscopy of YFP-tagged GR, was unaffected. Transactivation and transrepression were markedly impaired; however, GR R477H did not act in a dominant-negative manner, that is, did not prevent cell death, when introduced into a GC-sensitive cell line by retroviral gene transfer. Contrary to another GR heterozygous, but GC-sensitive, T-ALL model (CCRF-CEM), Jurkats expressed lower basal GR levels and did not autoinduce their GR, as revealed by 'real-time' RT-PCR and immunoblotting. Absent GR auto-induction could not be restored by transgenic GR and, hence, was not caused by reduced basal GR levels. Thus, inactivation of one GR gene results in haploinsufficiency if associated with lack of GR auto-induction.

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Section: Resultsmentioning

confidence: 99%

Glucocorticoid receptor heterozygosity combined with lack of receptor auto-induction causes glucocorticoid resistance in Jurkat acute lymphoblastic leukemia cells

et al. 2004

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“…The specific function of these two mRNAs has not yet been determined but some preliminary observations indicate that they both code for estrogen receptors: their stimulation by estradiol is parallel, they both hybridize, in stringent conditions, with probes containing DNA or hormone binding domains (data not shown). In other species, the presence of multiple steroid receptor mRNA has also been described: in Xen0pu.s four ER mRNAs from 2.5 to 9 kb (Weiler et al, 1987) in rat and man respectively two and three glucocorticoid receptor mRNAs from 4.8 to 7.1 kb (Hollenberg et al, 1985;Miesfeld et al, 1986). Progesterone receptor mRNA seems to be the more heterogeneous with Male rainbow trout (600-900 g) were injected with E, (1.5 mg/kg).…”

Section: Discussionmentioning

confidence: 98%

“…However, recent works show that two forms of human progesterone receptor (hPR), differing in their N-terminal region and proceeding from two classes of hPR mRNAs, exhibit different functional properties (Kastner et al, 1990). Cloning of several steroid receptor's genes reveals that these mRNAs are likely to be transcribed from a unique gene (Huckaby et al, 1987;Ponglikitmongkol et al, 1988;Kuiper et al, 1989) and they might result from the use of different transcription initiation sites (Kastner et al, 1990) or of different polyadenylation sites (Hollenberg et al, 1985). They can also arise from a differential splicing of the same primary transcript (Mitsuhashi et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

In vivo estrogen induction of hepatic estrogen receptor mRNA and correlation with vitellogenin mRNA in rainbow trout

Pakdel

Féon

Gac

et al. 1991

Molecular and Cellular Endocrinology

160

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SummaryWe have previously described the cloning, sequencing and in vitro expression of a full-length rainbow trout estrogen receptor cDNA (rtER cDNA). This full cDNA randomly labelled was used to study the estrogen induction of hepatic rtER mRNA in correlation with vitellogenin (Vg) mRNA in different physiolo~cal situations.In this paper, we show that in the liver two mRNA species are under hormonal control and their level increases about g-fold after estrogen stimulation.These two mRNAs are expressed and induced in the liver as early as the hatching stage in correlation with the expression of Vg mRNA. A long-term analysis of rtER mRNA after estradiol (E2) injection shows a transient induction of the nuclear ER and its mRNA which recover to the basal level after 2 weeks. Nevertheless, a memory effect was observed on the expression of the Vg gene which does not appear to be directly related to the estrogen receptor level.

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“…The effects of glucocorticoids are mediated through the GRa isoform (27) that resides in the cytoplasm in absence of hormone. Several investigations have shown that reductions in the number of GRa molecules/cell result in a decrease in glucocorticoid sensitivity (9 -11, 38, 39).…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid receptor transcriptional isoforms and resistance in multiple myeloma cells

Sánchez-Vega

Krett

Rosen

et al. 2006

Molecular Cancer Therapeutics

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Although glucocorticoids play an important role in the treatment of multiple myeloma, some patients do not respond or develop resistance. The glucocorticoid receptor (GR), a single gene, mediates the effects of glucocorticoids. Using a model system of a multiple myeloma cell line sensitive to glucocorticoids and its early and late resistant variants, we have analyzed mutations in the GR gene, detected the presence of different transcriptional isoforms, quantified their levels of expression, and identified the promoters that regulate their expression.

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Primary structure and expression of a functional human glucocorticoid receptor cDNA

Cited by 1,740 publications

References 63 publications

Glucocorticoid receptor heterozygosity combined with lack of receptor auto-induction causes glucocorticoid resistance in Jurkat acute lymphoblastic leukemia cells

Glucocorticoid receptor heterozygosity combined with lack of receptor auto-induction causes glucocorticoid resistance in Jurkat acute lymphoblastic leukemia cells

In vivo estrogen induction of hepatic estrogen receptor mRNA and correlation with vitellogenin mRNA in rainbow trout

Glucocorticoid receptor transcriptional isoforms and resistance in multiple myeloma cells

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