Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The changes of glucocorticoid receptor (GR) during the heat shock response have been studied using a human osteosarcoma cell line (HOS-8603) as the model. The expression of the heat shock protein 70 (hsp70) mRNA in HOS-8603 cells has been enhanced markedly after a heat treatment at 43 degrees C for 30 min. A mild thermal pretreatment (42 degrees C for 1 h) protects the HOS-8603 cells against a subsequent heat challenge (46 degrees C). This induced thermotolerance is reflected by the increase of cell viability of HOS-8603 cells. The GR binding activity in HOS-8603 cells decreased rapidly after the heat treatment at 43 degrees C; only 42.61% of controls were detected 60 min after the heat treatment. However, there was no significant change in the dissociation constant value (Kd). These results indicate that the heat shock induce not only the heat shock mRNA expression, but also the rapid reduction in GR binding activity, suggesting that there might be a functional relationship between GR action and the heat shock response.
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PMID:Effects of heat shock on glucocorticoid receptor. 791

HOS-8603 is a newly established human osteosarcoma cell line with phenotypic characteristics of osteoblasts. When these cells were grown in monolayer culture in the presence of dexamethasone (Dex) or retinoic acid (RA), there was a significant inhibition of proliferation in a concentration-dependent manner. The combined effects of Dex and RA depended upon the concentrations: at low concentrations (< 10 nM) the effects of Dex and RA were additive, whereas at high concentrations the effects were antagonistic. Anchorage-independent growth studies performed in methylcellulose culture indicated that Dex or RA inhibited colony formation by HOS-8603 cells. Treatment of HOS-8603 cells with 100 nM Dex induced alkaline phosphatase activity in a time-dependent manner, reaching a maximum of about 6.5-fold over basal levels. All these effects of Dex on HOS-8603 cells could be reversed by RU 486, a potent antiglucocorticoid. Based upon saturation of specific binding and Scatchard plot analysis, we demonstrated that a saturable, high-affinity glucocorticoid receptor (GR) existed in HOS-8603 cells, suggesting that the effects of glucocorticoids on HOS-8603 cells are mediated by the specific GR. Finally, we further investigated the homologous and heterologous regulation of GR in HOS-8603 cells. Treatment of these cells with Dex led to a time-dependent decrease in GR concentrations. This homologous GR downregulation occurred not only at the level of hormone binding but also at the level of GR mRNA. In contrast, RA was capable of increasing GR concentrations in a concentration- and time-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of retinoic acid and dexamethasone on proliferation, differentiation, and glucocorticoid receptor expression in cultured human osteosarcoma cells. 799 82

Previously, it has been found that glucocorticoid receptor (GR) binding activity decreased rapidly during heat shock response in HOS-8603, a human osteosarcoma cell line. In this study, The relationship between the induction of heat shock proteins (HSPs) and the decrease in GR was further studied in the same cell line. It was found that even though quercetin could specifically inhibit the expression of hsp90 alpha and hsp70 mRNA, it could not prevent GR from the decrease in response to the heat shock treatment. This represents the first reported evidence that the induction of HSPs and the decrease in GR during heat shock response were 2 independent biological events. The results of the present study further showed that although the heat shock treatment alone had no effects on alkaline phosphatase (AKP) activity, it could completely block the induction of AKP activity in HOS-8603 cells by dexamethasone (Dex), a synthetic glucocorticoid. These results demonstrate that the heat shock-induced alteration in GR was accompanied by a decrease in GR functional activity. Furthermore, when the induction of HSPs was inhibited by the treatment of cells with quercetin, the stimulatory effects of Dex on AKP activity could still be inhibited completely by the heat shock treatment. The results of this part, on the basis of GR functional activity, further demonstrate that quercetin could not inhibit the heat shock-induced decrease in GR even though it could inhibit the induction of HSPs. To clarify further the effects of quercetin alone on GR binding activity in HOS-8603 cells, the regulation of GR by quercetin was also studied. It was found for the first time that quercetin could down-regulate GR in a time-dependent manner significantly, and that the down-regulation of GR by quercetin in HOS-8603 cells paralelled with a decrease in glucocorticoid-mediated functional responses, suggesting that the down-regulation of GR by quercetin is of biological significance.
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PMID:Relationship between the induction of heat shock proteins and the decrease in glucocorticoid receptor during heat shock response in human osteosarcoma cells. 874 75

The glucocorticoid receptor (GR) can both activate and repress transcription of target genes by interaction with specific genomic response elements, glucocorticoid response elements (GREs). Activation of transcription is usually the result of the direct interaction between GR and the GRE, whereas GR-mediated transcription repression is either the result of the indirect action of GR, mediated by a response element as a result of protein.protein interaction or by an occlusion mechanism in which GR displaces a general or regulatory transcription factor. A specific mutation of rat GR, K461A, has previously been described to transform the indirect protein.protein interaction-dependent transrepressive effect of GR into an activating function (Starr, D. B., Matsui, W., Thomas, J. R., and Yamamoto, K. R. (1996) Genes Dev. 10, 1271-1283). In HOS D4 and COS7 cells, this mutation was shown to transform the transrepressive effect of wild-type GR, acting on reporter constructs containing the composite GRE from the proliferin gene (plfG) or the negative tethering GRE from the collagenase A promoter (colA), into an activating function. In contrast, the K461A mutation had no effect on the transrepressive effect of GR on the human osteocalcin gene in which repression apparently occurs through the binding of GR to a negative GRE that overlaps the TATA box. The transrepressive function, typically 40% of the basal level in the absence of hormone, required only the isolated DNA-binding domain of wild type or mutant GR and was independent of the nature of transactivation domain. Thus, mutation of rat GR at position 461 differentiates between transrepressive functions of GR dependent on GR.DNA interaction (repression by occlusion) and GR.protein interaction (active repression).
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PMID:The rat glucocorticoid receptor mutant K461A differentiates between two different mechanisms of transrepression. 926 Nov 12

The effect of gamma interferon (IFN) on glucocorticoid receptor (GR) expression was studied in HOS-8603 cells, a human osteogenic sarcoma cell line. Treatment of HOS-8603 cells with IFN resulted in down-regulation of GR number, with no change in the binding affinity for glucocorticoids. The maximum decrease in receptor binding was evident at 10 IU/ml IFN concentration. Time-course studies revealed that the effect reached a maximum at 36 h treatments. To clarify the molecular basis for the down-regulation of GR by IFN, change in GR mRNA levels was further investigated by RNA blot hybridization analysis. It was found that there also existed a time-dependent decrease in GR mRNA levels in HOS-8603 cells after treatment with IFN. In the presence of IFN, the inhibitory effect of glucorticoids on HOS-8603 cell proliferation was blunted. Moreover, the induction of alkaline phosphatase (AKP) activity by glucocorticoids was attenuated in response to IFN treatment. These data suggest that IFN may influence GR activity which at least partially occurs at mRNA levels, and that the decrease in receptor activity in HOS-8603 cells parallels with the decrease in glucocorticoid-mediated functional responses.
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PMID:Gamma interferon down-regulates glucocorticoid receptor expression and attenuates hormone action in a human osteosarcoma cell line. 2115 63