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)

We have previously shown that insulin-like growth factor II (IGF-II) is produced by bone cells and that IGF-II stimulates cell proliferation and collagen synthesis in bone cells. We now extend these in vitro findings by demonstrating specific IGF-II binding to bone cells derived from newborn mouse calvaria and embryonic chick calvaria. The kinetics of [125I] IGF-II binding in embryonic chick calvaria cells showed time and temperature dependence. Scatchard analysis of [125I]IGF-II binding to chick calvaria cells showed an apparent Kd of 1.4 x 10(-10) M, with a calculated receptor site concentration of 40,000/cell. The specificity characteristics showed that IGF-II was significantly more potent than IGF-I or insulin in displacing IGF-II tracer. Competition for binding of [125I]IGF-II by unlabeled IGF-II showed a dose-dependent displacement between 0.5 and 25 ng/ml. Fifty percent displacement of [125I]IGF-II binding to chick and mouse calvarial cells was achieved at 1-2 ng/ml; 90% of specific binding of [125I]IGF-II was displaceable in the presence of 125 ng/ml of unlabeled IGF-II. IGF-I showed less than 5% cross reactivity for displacement of [125I]IGF-II binding to chick and mouse bone cells. Type II receptor inhibitory antibodies, R-II-PAB1 inhibited the binding of [125I]IGF-II to mouse bone cells and H-35 rat hepatoma cells (which contain type II but not type I receptors) in a dose-dependent manner. R-II-PAB1 also inhibited basal cell proliferation as well as IGF-II-, IGF-I-, and fibroblast growth factor (FGF)-induced cell proliferation in mouse bone cells. In chick calvaria bone cells and TE89 human osteosarcoma cells, R-II-PABI inhibited neither binding of [125I]IGF-II nor IGF-II-induced cell proliferation. These results together with our findings that IGF-II increased chick bone cell proliferation in the presence of maximal doses of IGF-I suggest that at least part of the mitogenic action of IGF-II is mediated through type II rather than type I receptors in bone cells.
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PMID:Characterization of the receptor for insulin-like growth factor II in bone cells. 254 14

Stimulation of bone by low-energy electromagnetic fields (EMFs) may prove to be an efficient therapy for skeletal disorders. The study discussed in this article demonstrates that an EMF of 15.3 Hz can increase the proliferation rate of an osteosarcoma cell line, TE-85. The increase in cell proliferation was associated with an increase in binding sites for insulin-like growth factor II and an increase in mitogen activity in culture media.
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PMID:Growth factors and electromagnetic fields in bone. 792 37

Genomic imprinting is the parental allele specific expression of genes and has recently been shown to occur in humans. Evidence for a role for genomic imprinting in human cancer comes from the finding of preferential retention of paternal alleles in embryonal tumors undergoing loss of heterozygosity, e.g., Wilms' tumor and osteogenic sarcoma. Recent studies have demonstrated imprinting of the insulin-like growth factor II gene at 11p15 in normal individuals, with the paternally inherited allele expressed and the maternal allele silent. It has been shown that normal imprinting is relaxed, and gene expression is biallelic in a majority of Wilms' tumors which retain heterozygosity at this locus. In this study an intragenic ApaI polymorphism is used to examine imprinting of the insulin-like growth factor II gene in hepatoblastoma. Three of 5 tumors studied were heterozygous and hence informative. All cases showed monoallelic expression of the insulin-like growth factor II gene, indicating maintenance of normal imprinting at this locus.
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PMID:Maintenance of genomic imprinting at the IGF2 locus in hepatoblastoma. 840 61

Extracellular calcium concentration is critically important for normal function of the body. Recently, reports have shown that cells derived from parathyroid glands contain an extracellular calcium receptor that is responsive to changes in extracellular calcium. Bone is intimately involved in calcium homeostasis; therefore, we sought to test the hypothesis that extracellular calcium has direct effects on bone cells. Extracellular calcium was increased by the addition of varying concentrations of CaCl2 (0.4-2.0 mM) to the control medium. An increase in extracellular calcium increased cell proliferation, as assessed by 3H-thymidine incorporation, in a number of cell types including normal human bone cells derived from vertebrae (HBV155) and a number of human osteosarcoma cell lines. The increase in cell proliferation by elevated CaCl2 was dose dependent, whereas MgCl2 was not effective at the doses tested (up to 2 mM added MgCl2). To test the hypothesis that the mitogenic activity of elevated extracellular calcium involved a growth factor, levels of insulin-like growth factor II (IGF-II) were measured in the conditioned medium of HBV155 cells by radioimmunoassay after removal of binding proteins by size exclusion chromatography. The effects of an increase in extracellular calcium by 1 mM were: 1) increased culture media levels of IGF-II within 1 h of treatment, 2) the increase in IGF-II levels reached a maximum after 8 h of treatment, and 3) IGF-II levels were still elevated after 24 h of treatment. Furthermore, a blocking monoclonal antibody against IGF-II abolished the increased cell proliferation in HBV155 cells following elevation of extracellular calcium. Taken together, these findings suggest that an increase in extracellular calcium results in an increase in IGF-II which is required for the subsequent increase in cell proliferation.
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PMID:Effects of extracellular calcium on insulin-like growth factor II in human bone cells. 859 42

Gene hypomethylation and hypermethylation can lead to a loss of genetic imprinting in malignancies. The mechanism responsible for overexpression of the imprinted insulin-like growth factor II (IGF2) gene has not been investigated in osteosarcoma. In this study, the expression levels, imprinting status, and the extent of cytosine methylation of the IGF2 gene was evaluated in 20 of 24 cases of osteosarcoma using immunohistochemistry, reverse transcriptase polymerase chain reaction, restriction fragment length polymorphism, and bisulfite genomic sequencing. Promoter use analysis indicated that P3- and P4-derived messenger RNAs were more highly expressed than P1 transcripts in the osteosarcoma samples. Loss of imprinting of IGF2 was observed in 3 of 20 of the osteosarcoma samples, but this was not associated with IGF2-specific transcripts. Methylation analysis revealed that the methylation patterns of the differentially methylated region of IGF2 were not uniform, regardless of IGF2-P3 expression. However, the average degree of methylation of the 14 CpG sites in the IGF2-P3 promoter was significantly lower in osteosarcoma samples with P3 transcripts than in osteosarcoma samples without P3 expression (P < .05). This observation was also observed in nontumor samples. These data suggest that hypomethylation of the IGF2-P3 promoter correlates with expression of P3 transcripts in osteosarcoma. Furthermore, elevated IGF2-P3 expression in osteosarcoma tissues is due to P3 promoter hypomethylation, which may represent an early event in progression of osteosarcoma.
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PMID:Hypomethylation of the P3 promoter is associated with up-regulation of IGF2 expression in human osteosarcoma. 1942 70