Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogens have profound effects on bone metabolism. Cellular responses to estrogens are mediated by estrogen receptors (ERs) which belong to the nuclear receptor superfamily. Two estrogen receptors, ERalpha and ERbeta, have been cloned. Previously expression of ERalpha has been shown in osteoblasts. Here we demonstrate that the transcript for ERbeta can be detected in the human osteosarcoma cell lines (MG-63 and SaOS-2) and in cultured human osteoblast-like cells. We also show that ERbeta protein is present in nuclear extracts from these cells. Furthermore, ERbeta immunoreactivity is found in sections of murine and human bone. Murine and human osteoblast and osteocyte nuclei are immunoreactive for ERbeta. Osteoclasts are also ERbeta immunoreactive but the staining is mainly cytoplasmic. The present study demonstrates that ERbeta is present in all the cellular compartments involved in bone formation and bone resorption, both in human and in murine bone tissue.
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PMID:Expression and localization of estrogen receptor-beta in murine and human bone. 1035

Estrogens and selective estrogen receptor modulators (SERMs) interact with estrogen receptor (ER) alpha and beta to activate or repress gene transcription. To understand how estrogens and SERMs exert tissue-specific effects, we performed microarray analysis to determine whether ERalpha or ERbeta regulate different target genes in response to estrogens and SERMs. We prepared human U2OS osteosarcoma cells that are stably transfected with a tetracycline-inducible vector to express ERalpha or ERbeta. Western blotting, immunohistochemistry, and immunoprecipitation studies confirmed that U2OS-ERalpha cells synthesized only ERalpha and that U2OS-ERbeta cells expressed exclusively ERbeta. U2OS-ERalpha and U2OS-ERbeta cells were treated either with 17beta-estradiol (E2), raloxifene, and tamoxifen for 18 h. Labeled cRNAs were hybridized with U95Av2 GeneChips (Affymetrix). A total of 228, 190, and 236 genes were significantly activated or repressed at least 1.74-fold in U2OS-ERalpha and U2OS-ERbeta cells by E2, raloxifene, and tamoxifen, respectively. Most genes regulated in ERalpha cells in response to E2, raloxifene, and tamoxifen were distinct from those regulated in ERbeta cells. Only 38 of the 228 (17%) genes were regulated by E2 in both U2OS-ERalpha and U2OS-ERbeta cells. Raloxifene and tamoxifen regulated only 27% of the same genes in both the ERalpha and ERbeta cells. A subset of genes involved in bone-related activities regulated by E2, raloxifene, and tamoxifen were also distinct. Our results demonstrate that most genes regulated by ERalpha are distinct from those regulated by ERbeta in response to E2 and SERMs. These results indicate that estrogens and SERMs exert tissue-specific effects by regulating unique sets of targets genes through ERalpha and ERbeta
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PMID:Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. 1469 72

Estrogens exert many important effects in bone, a tissue that contains both estrogen receptors alpha and beta (ERalpha and ERbeta). To compare the actions of these receptors, we generated U2OS human osteosarcoma cells stably expressing ERalpha or ERbeta, at levels comparable with those in osteoblasts, and we characterized their response to 17beta-estradiol (E2) over time using Affymetrix GeneChip microarrays to determine the expression of approximately 12,000 genes, followed by quantitative PCR verification of the regulation of selected genes. Of the approximately 100 regulated genes we identified, some were stimulated by E2 equally through ERalpha and ERbeta, whereas others were selectively stimulated via ERalpha or ERbeta. The E2-regulated genes showed three distinct temporal patterns of expression over the 48-h time course studied. Of the functional categories of the E2-regulated genes, most numerous were those encoding cytokines and factors associated with immune response, signal transduction, and cell migration and cytoskeleton regulation, indicating that E2 can exert effects on multiple pathways in these osteoblast-like cell lines. Of note, E2 up-regulated several genes associated with cell motility selectively via ERbeta, in keeping with the selective E2 enhancement of the motility of ERbeta-containing cells. On genes regulated equally by E2 via ERalpha or ERbeta, the phytoestrogen genistein preferentially stimulated gene expression via ERbeta. These studies indicate both common as well as distinct target genes for these two ERs, and identify many novel genes not previously known to be under estrogen regulation.
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PMID:Transcriptional profiling of estrogen-regulated gene expression via estrogen receptor (ER) alpha or ERbeta in human osteosarcoma cells: distinct and common target genes for these receptors. 1503 14

Estrogens (E) and mechanical strain (MS) exert direct effects on osteoblast activity, with good evidence of interactions between their respective effects. Osteoblasts express both forms of estrogen receptors (ER) ERalpha and ERbeta, and previous studies have suggested a specific role for each receptor. Therefore, our working hypothesis was that the interactions between E and MS on osteoblast activity vary depending on which ER is preferentially activated. Using human osteosarcoma cells U2OS stably transfected either with ERalpha or ERbeta, we evaluated the effects of cyclical cell loading on a F-3000 Flexercell Strain Unit (1.5% elongation, 10 min/day) in presence of estradiol (E2) 10(-8) M or not. The original U2OS cell line, which does not express ER, was characterized by low alkaline phosphatase (AP) activity. In both U2OS-ERalpha and U2OS-ERbeta cell lines, MS induced similar increases in AP activity and gene expression as measured by real-time quantitative RT-PCR, and a decrease in type I collagen gene expression. MS and E2 had a synergistic effect on AP activity as compared to each stimulus alone. No change in proliferation rate was observed. Neither proliferation nor differentiation of the original U2OS cell line was altered by strain or E2. In summary, our data showing differences in response to MS between the U2OS with no ER expression and the U2OS-ERalpha or -ERbeta cell lines provide additional evidence that ER plays a critical role in mechanotransduction. However, we were not able to demonstrate that interactions between E and MS were dependent on ER type in U2OS osteosarcoma cells.
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PMID:Interactions between estrogen and mechanical strain effects on U2OS human osteosarcoma cells are not influenced by estrogen receptor type. 1554 38

Estrogens modulate the transcription of sensitive genes either via binding of the activated ER to responsive elements in their promoter region or via binding of the activated ER to transcription factors like NFkappaB. In this study we have analyzed the effects of the phytoestrogens daidzein, coumestrol and genistein in promoter-specific reporter gene systems. The dose-dependent ability to stimulate an ERE-bearing reporter in MVLN breast cancer cells was compared to the dose-dependent ability to repress the IL-1beta-stimulated reporter in U2OS osteosarcoma cells. Coumestrol, daidzein and genistein stimulate the expression of the ERE-dependent reporter in MVLN cells and repress the activity of the IL-6 promoter in U2OS cells in a dose-dependent manner. Interestingly, the relative potency of all phytoestrogens to repress the activity of the IL-6 promoter in U2OS cells was much higher than their potency to stimulate the ERE-dependent reporter in MVLN cells. We assume that the demonstrated promoter-specific potency therefore could be an important mechanism to explain a tissue-specific action of some of these compounds.
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PMID:Analysis of the promoter-specific estrogenic potency of the phytoestrogens genistein, daidzein and coumestrol. 1649 57