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)

Integrin alpha2beta1 is a heterodimeric transmembrane receptor for collagens. In osteogenic cells the expression of alpha2beta1 integrin is induced by both Kirsten sarcoma virus and chemical transformation. The association of alpha2 integrin with transformed cell phenotype was studied further by testing the effects of two tumor promoters, 12-O-tetradecanoylphorbol 13-acetate (TPA) and okadaic acid (OA), on human MG-63 osteosarcoma cells. TPA, an activator of protein kinase C, increased the cell surface expression of alpha2 integrin and the corresponding mRNA levels. Nuclear run-on assays indicated that TPA activated the transcription of alpha2 integrin gene. TPA also slightly increased the expression of alpha3 integrin but had no effect on the transcription of alpha5, alphav, or beta1 integrin subunits. OA, an inhibitor of serine/threonine phosphatases, increased alpha2 integrin gene transcription and mRNA levels, but in contrast to TPA, OA decreased alpha3 integrin expression. The increased expression of alpha2 integrin on TPA-treated MG-63 cells led to faster cell spreading on type I collagen. Our results link the enhanced transcription of alpha2 integrin gene to tumor progression and show the independent regulation of alpha2 integrin compared to other integrin genes.
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PMID:Transcription of alpha2 integrin gene in osteosarcoma cells is enhanced by tumor promoters. 971 43

Prior studies have demonstrated that the pineal hormone, melatonin, can stimulate chloramphenicol acetyltransferase activity in Drosophila SL-3 cells transfected with a chloramphenicol acetyltransferase reporter construct containing the response element of rat bone sialoprotein (BSP). Based on these findings, studies were performed to determine whether melatonin could similarly modulate the expression of BSP in two cell lines, the MC3T3-E1(MC3T3) pre-osteoblast and rat osteoblast-like osteosarcoma 17/2.8 cell. Initial studies demonstrated that MC3T3 cells grown in the presence of 50 nM melatonin underwent cell differentiation and mineralization by day 12 instead of the 21-day period normally required for cells grown in untreated media. Melatonin increased gene expression of BSP and the other bone marker proteins, including alkaline phosphatase (ALP); osteopontin; secreted protein, acidic and rich in cysteine; and osteocalcin in MC3T3 cells in a concentration-dependent manner. Levels of melatonin as low as 10 nM were capable of stimulating transcription of these genes when cells were grown in the presence of beta-glycerophosphate and ascorbic acid. Under these conditions, melatonin induced gene expression of the bone marker proteins; however, this does not occur until the 5th day after seeding the culture dishes. Thereafter, MC3T3 cells responded to melatonin within 2 h of treatment. The fully differentiated rat osteoblast-like osteosarcoma 17/2.8 cells responded rapidly to melatonin and displayed an increase in the expression of BSP, ALP, and osteocalcin genes within 1 h of exposure to the hormone. To determine whether melatonin-induced osteoblast differentiation and bone formation are mediated via the transmembrane receptor, MC3T3 cells were treated in the presence and absence of melatonin with either luzindole, a competitive inhibitor of the binding of melatonin to the transmembrane receptors, or pertussis toxin, an uncoupler of G(i) from adenylate cyclase. Both luzindole and pertussis toxin were shown to reduce melatonin-induced expression of BSP and ALP. These results demonstrate, for the first time, that the pineal hormone, melatonin, is capable of promoting osteoblast differentiation and mineralization of matrix in culture and suggest that this hormone may play an essential role in regulating bone growth.
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PMID:Melatonin promotes osteoblast differentiation and bone formation. 1041 30

Clones for a novel transmembrane receptor termed FGFRL1 were isolated from a subtracted, cartilage-specific cDNA library prepared from chicken sterna. Homologous sequences were identified in other vertebrates, including man, mouse, rat and fish, but not in invertebrates such as Caenorhabditis elegans and Drosophila. FGFRL1 was expressed preferentially in skeletal tissues as demonstrated by Northern blotting and in situ hybridization. Small amounts of the FGFRL1 mRNA were also detected in other tissues such as skeletal muscle and heart. The novel protein contained three extracellular Ig-like domains that were related to the members of the fibroblast growth factor (FGF) receptor family. However, it lacked the intracellular protein tyrosine kinase domain required for signal transduction by transphosphorylation. When expressed in cultured cells as a fusion protein with green fluorescent protein, FGFRL1 was specifically localized to the plasma membrane where it might interact with FGF ligands. Recombinant FGFRL1 protein was produced in a baculovirus system with intact disulfide bonds. Similar to FGF receptors, the expressed protein interacted specifically with heparin and with FGF2. When overexpressed in MG-63 osteosarcoma cells, the novel receptor had a negative effect on cell proliferation. Taken together our data are consistent with the view that FGFRL1 acts as a decoy receptor for FGF ligands.
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PMID:Characterization of FGFRL1, a novel fibroblast growth factor (FGF) receptor preferentially expressed in skeletal tissues. 1281 49

Osteosarcoma (OS) and Ewing sarcoma (ES) are the two most common types of primary bone cancer, which mainly affect children and young adults. Despite intensive multi-modal treatment, the survival of both OS and ES has not improved much during the last decades and new therapeutic options are awaited. One promising approach is the specific targeting of transmembrane receptor tyrosine kinases (RTKs) implicated in these types of bone cancer. However, despite encouraging in vitro and in vivo results, apart from intriguing results of Insulin-like Growth Factor-1 Receptor (IGF-1R) antibodies in ES, clinical studies are limited or disappointing. Primary resistance to RTK inhibitors is frequently observed in OS and ES patients, and even patients that initially respond well eventually develop acquired resistance. There are, however, a few remarks to make concerning the current set-up of clinical trials and about strategies to improve RTK-based treatments in OS and ES. This review provides an overview concerning current RTK-mediated therapies in OS and ES and discusses the problems observed in the clinic. More importantly, we describe several strategies to overcome resistance to RTK inhibitors which may significantly improve outcome of OS and ES patients.
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PMID:Targeting receptor tyrosine kinases in osteosarcoma and Ewing sarcoma: current hurdles and future perspectives. 2458 52

Osteosarcoma (OSA) is the most common primary tumor of the bone. Resistance to chemotherapy and the fast rapid development of metastatic lesions are major issues responsible for treatment failure and poor survival rates in OSA patients. Tetraspanins comprise a family of transmembrane receptor glycoproteins that affect tumor cell migration through tetraspanin-integrin interaction. The present study focused on a four-pass transmembrane protein gene, transmembrane protein 35 (TMEM35) gene, and examined its role in the growth, migration and cell cycle progression of OSA cells. In addition, the study discussed whether the TMEM35 gene, which encodes the TMEM35 protein, may be a potential therapeutic target for OSA. In the current study, reverse transcription-quantitative polymerase chain reaction was performed to examine TMEM35 expression in OSA and matched healthy tissues. Small interfering RNAs (siRNAs) were transfected into SaOS2 and U2OS cells to knockdown the TMEM35 expression. Soft-agar colony formation assay was performed to evaluate cell growth, and cell cycle progression was analyzed by flow cytometry. Wound-healing and Boyden chamber assays were also performed to investigate cell invasion and migration by the SaOS2 and U2OS cells. TMEM35 protein was analyzed in a functional protein interaction networks database (STRING database) to predict the functional interaction partner proteins of TMEM35. The results indicated that TMEM35 was abnormally expressed in OSA tissues. Of the 37 examined patients, TMEM35 expression was significantly increased in the OSA tissues of 24 patients (64.86%; P<0.05), when compared with the expression in normal tissues. Furthermore, TMEM35 knockdown following transfection with siRNAs inhibited the colony formation ability of SaOS2 and U2OS cells in soft agar. Flow cytometric analysis also revealed that TMEM35 knockdown by RNA interference may result in G1 phase arrest and a decreased cell population at the S phase. TMEM35 knockdown inhibited cell migration in SaOS2 and U2OS cells in wound-healing assays. In conclusion, TMEM35, a member of the tetraspanin family, serves an important role in the growth of OSA cells.
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PMID:Downregulation of coding transmembrane protein 35 gene inhibits cell proliferation, migration and cell cycle arrest in osteosarcoma cells. 2744 47