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)

Bone sialoprotein (BSP) is a major noncollagenous protein of the mineralized bone extracellular matrix that has been implicated in the nucleation of hydroxyapatite. Recent studies have shown that BSP is also expressed by osteotropic cancers suggesting BSP might play a role in the pathogenesis of bone metastases. The present study investigates regulation of BSP transcription in rat osteosarcoma ROS 17/2.8 cells by flavonoids: genistein (an inhibitor of protein tyrosine kinases), daidzein (an inactive compound of genistein), flavone, and flavanone. Genistein, daidzein, and flavone (50 microM) increased steady state levels of BSP mRNA about 1.7-fold at 12 h. From transient transfection assays using various sized BSP promoter-luciferase constructs, genistein increased luciferase activities within 12 h. Constructs including the promoter sequence nucleotides (nts) -116 to -43 (pLUC3) were found to enhance transcriptional activity approximately 2.6-fold in ROS 17/2.8 cells treated with genistein (50 microM). Daidzein, flavone, and flavanone (50 microM) also increased luciferase activities. In contrast, the tyrosine kinase inhibitors, herbimycin A and lavendustin A, which do not have a flavonoid structure, did not stimulate BSP transcription. Transcriptional stimulation by genistein was almost completely abrogated in a construct that included 2 bp mutations in the inverted CCAAT box. A monoclonal antibody against NF-YA, a CCAAT box-binding transcription factor, inhibited formation of DNA-NF-Y protein complex in gel shift assays formed by nuclear extracts of ROS 17/2.8 cells. These data suggest that the inverted CCAAT box is required for flavonoid-induced BSP expression and that the stimulatory action is dependent on the flavone structure and does not involve an inhibitory action on protein tyrosine kinase.
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PMID:Activation of bone sialoprotein gene transcription by flavonoids is mediated through an inverted CCAAT box in ROS 17/2.8 cells. 1211 14

Plant-derived phytoestrogens and estrogens in hormone replacement therapies have overlapping yet sometimes divergent effects on the incidence of breast cancer and osteoporosis. Using human MCF-7 breast carcinoma and G-292 osteosarcoma cell lines, it was investigated whether the phytoestrogens genistein and daidzein affect reporter gene transcription via the estrogen receptors (ERs) ERalpha and ERbeta1 as well as whether they affect the expression of estrogen-responsive genes in MCF-7 cells and the secretion of the cytokine IL-6 from G-292 cells. The results showed that genistein and daidzein potently trigger transactivation with ERbeta1 from estrogen response element-reporter genes (EC50s of 1.7-16 nM) although they were 400- to 600-fold less potent than 17beta-estradiol (E2) (EC50 of 0.02-0.04 nM). E2 was the only potent activator of ERalpha (EC50 of 0.1-0.4 nM). The rank order potency (E2 > genistein > daidzein) is maintained in MCF-7 cells as well as G-292 cells with both receptor subtypes, with a strong receptor selectivity of the phytoestrogens for ERbeta1 over ERalpha. Genistein and daidzein increased the expression of estrogen-responsive genes in MCF-7 cells. Daidzein, like E2, inhibited IL-1beta- and hormone-mediated IL-6 secretion from G-292 cells. The results provide a basis for understanding how dietary phytoestrogens protect bone without increasing the risks for breast cancer.
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PMID:Phytoestrogens activate estrogen receptor beta1 and estrogenic responses in human breast and bone cancer cell lines. 1726 78