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)

We have identified and characterized a novel human estrogen receptor (ER) beta isoform, ERbetacx, which is truncated at the C-terminal region but has an extra 26 amino acids due to alternative splicing. The ERbetacx transcript is expressed in testis, ovary, thymus and prostate as well as in human cultured cell lines such as HEC-1, HOS-TE85 and Saos-2 cells. ERbetacx protein is also immunodetectable in these human cells. Biochemical analysis reveals that the average dissociation constants ( K d) of ERalpha and ERbeta for 17beta-estradiol (E2) are 0.2 and 0.6 nM respectively, but ERbetacx has no ligand binding ability. ERalpha and ERbeta proteins bind to the estrogen response element, whereas ERbetacx does not form any shifted complex in gel shift assays. In a transient expression assay, ERbetacx shows no ligand-dependent transactivation ability of a basal promoter and also cannot interact with a cofactor, TIF1alpha, in the presence or absence of E2. ERbetacx preferentially forms a heterodimer with ERalpha rather than that with ERbeta, inhibiting DNA binding by ERalpha. Interestingly, however, it shows a significant dominant negative activity only against ERalpha transactivation. Thus, this study indicates that ERbetacx potentially inhibits ERalpha-mediated estrogen action and that alternative splicing of the C-terminal region and its inhibitory properties are characteristic of several members of nuclear receptor isoforms.
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PMID:Molecular cloning and characterization of human estrogen receptor betacx: a potential inhibitor ofestrogen action in human. 967 11

The effect of the proinflammatory cytokine interleukin (IL)-1beta on the cellular proliferation of human osteoblastic cells (SaM-1) and osteosarcoma-derived cells (SaOS-2, HOS, and MG-63) was examined. IL-1beta stimulated the proliferation of SaM-1 and MG-63 cells, but had no effect on that of SaOS-2 or HOS cells. Using reverse transcription-polymerase chain reaction (RT-PCR) analysis, the mRNA expression of IL-1 receptor type I (IL-1R1) was detected in SaM-1 and MG-63 cells consistently, but not in SaOS-2 or HOS cells in the proliferative stage. Neither the decoy inhibitory IL-1 receptor type II (IL-1R2) nor IL-1R antagonist mRNA was detected in any of the cell lines, suggesting that IL-1beta stimulated proliferation via IL-1R1. The IL-1beta -stimulated proliferation was inhibited by the MAPK kinase (MEK) inhibitor PD98059 but not by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 or the cyclooxygenase-2 specific inhibitor NS-398, suggesting that IL-1beta stimulated proliferation via MEK, without affecting prostaglandin E(2) synthesis. IL-1beta stimulated cellular proliferation but inhibited the synthesis of osteocalcin containing gamma-carboxylated glutamic acid (Gla-OSCAL). Both the increased proliferation and decreased Gla-OSCAL synthesis were suppressed by vitamin K(2) (VK(2)), which is a cofactor for gamma-carboxylase. Furthermore, the inhibitory effect of VK(2) on IL-1beta -stimulated proliferation was suppressed by warfarin. However, rifampicin the nuclear receptor steroid and xenobiotic receptor (SXR) ligand had no effect of IL-beta, suggesting that IL-1beta is involved in VK(2) dependent gamma-calboxylation but not SXR-activation. These results suggest that IL-1beta stimulated cellular proliferation via MEK and inhibited Gla-OSCAL synthesis, which were both inhibited by VK(2) via gamma-carboxylation.
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PMID:Inhibitory effect of vitamin K(2) on interleukin-1beta-stimulated proliferation of human osteoblasts. 2046 Jul 58