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), a major protein in the extracellular matrix of bone, is expressed almost exclusively by bone cells and by cancer cells that have a propensity to metastasize to bone. Previous studies have shown that v-src stimulates basal transcription of bsp in osteosarcoma (ROS 17/2.8) cells by targeting the inverted CCAAT element (ICE) in the proximal promoter. To identify possible downstream effectors of Src we studied the effects of the proto-oncogene c-jun, which functions downstream of Src, on basal transcription of bsp using transient transfection assays. Increased expression of endogenous c-Jun induced by the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate and ectopic expression of c-Jun increased basal transcription of chimeric reporter constructs encompassing the proximal promoter by 1.5-3-fold in ROS 17/2.8 osteosarcoma cells, with more modest effects in a normal bone cell line, RBMC-D8. The effects of c-Jun were abrogated by mutations in the ICE box and by co-expression of dominant negative nuclear factor Y, subunit A (NF-YA). The increase in bsp transcription did not require phosphorylation of c-Jun and was not altered by trichostatin treatment or by ectopic expression of p300/CREB-binding protein (CBP) or mutated forms lacking histone acetyltransferase (HAT) activity. Similarly, ectopic expression of p300/CBP-associated factor (P/CAF), which transduces p300/CBP effects, or of HAT-defective P/CAF did not influence the c-jun effects. Surprisingly, E1A, which competes with P/CAF binding to p300/CBP, also stimulated BSP transcription through NF-Y independently of c-jun, p300/CBP, and P/CAF. Collectively, these studies show that c-Jun and E1A regulate basal transcription of bsp in osteosarcoma cells by recruiting the NF-Y transcriptional complex to the ICE box in a mechanism that is independent of p300/CBP and P/CAF HAT activities.
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PMID:Recruitment of nuclear factor Y to the inverted CCAAT element (ICE) by c-Jun and E1A stimulates basal transcription of the bone sialoprotein gene in osteosarcoma cells. 1608 80

Purpose: The purpose of this study was to investigate the profile of histone deacetylase (HDAC) activity and expression in osteosarcoma cells and tissues from osteosarcoma patients and to examine the mechanism by which a histone deacetylase (HDAC) inhibitor, Trichostatin A (TSA), promotes the apoptosis of osteosarcoma cells. Methods: HDAC activity and histone acetyltransferase (HAT) activity were determined in nuclear extracts of MG63 cells, hFOB 1.19 cells and tissues from 6 patients with primary osteosarcoma. The protein expression of Class I HDACs (1, 2, 3 and 8) and the activation of the p53 signaling pathway were examined by Western blot. Cell growth and apoptosis were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) assay and flow cytometry, respectively. Results: Nuclear HDAC activity and class I HDAC expression were significantly higher in MG63 cells than in hFOB 1.19 cells, and a similar trend was observed in the human osteosarcoma tissues compared with the paired adjacent non-cancerous tissues. TSA significantly inhibited the growth of MG63 cells and promoted apoptosis in a dose-dependent manner through p53 signaling pathway activation. Conclusion: Class I HDACs play a central role in the pathogenesis of osteosarcoma, and HDAC inhibitors may thus have promise as new therapeutic agents against osteosarcoma.
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PMID:Histone Deacetylase Inhibitor Trichostatin a Promotes the Apoptosis of Osteosarcoma Cells through p53 Signaling Pathway Activation. 2787 82