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)

Normal and malignant osteoblast-like cells in culture have been shown to possess specific, high affinity receptors for epidermal growth factor (EGF). In this study, the mitogenic response to EGF was examined in a clonal line of a rat osteogenic sarcoma (UMR 106) and in osteoblast-rich newborn rat calvarial cells. Twenty-four hour treatment of UMR 106 cells with EGF in doses ranging from 10(-12) M to 2 X 10(-8) M stimulated the incorporation of [3H]thymidine and DNA synthesis in a dose-dependent manner. This short-term stimulatory effect was sustained in long-term culture with a dose-dependent increase in cell proliferation by calvarial cells. A lag period of 8 h occurred before significant stimulation of [3H]thymidine incorporation was observed. Commitment to increased incorporation of [3H]thymidine required a minimum of 6 h continuous incubation with EGF. These results establish the osteoblast as a target cell for EGF action on bone.
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PMID:Stimulation of DNA synthesis by epidermal growth factor in osteoblast-like cells. 660 68

The FM-2 cell line is a cloned, immortalized cell line derived from a human osteosarcoma. Conditioned medium from FM-2 cultures contains a factor which stimulates calcium mobilization from fetal rat bone organ cultures. Treated bones contain increased numbers of osteoclasts and decreased bone matrix. This factor has a molecular weight of approximately 29,000 as determined by gel filtration. Its biological activity is dependent on a protein moiety and is completely inhibited by calcitonin. Its synthesis by the FM-2 line is dependent on cell density and replenishment of fresh medium. This factor is not parathyroid hormone, a vitamin D metabolite, prostaglandin E, epidermal growth factor, or osteoclast-activating factor, all of which have bone-resorbing activities. Also, FM-2-conditioned medium inhibits collagen synthesis in fetal rat calvaria cells and decreases alkaline phosphatase levels in an osteoblastic cell line, and these two properties coelute with the calcium-mobilizing factor from a hydroxylapatite column. These biological products, synthesized by a cell line derived from a tumor, may represent physiological factors normally synthesized by a subpopulation of bone cells.
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PMID:New bone resorption stimulation factor elaborated by a human osteosarcoma cell line. 660 87

Hormonal control of plasminogen activator (PA) was studied in clonal rat osteogenic sarcoma cells which are phenotypically osteoblast, and in osteoblast-rich rat bone cell cultures. The bone-resorbing hormones (parathyroid hormone, prostaglandin E2, epidermal growth factor and 1,25-dihydroxyvitamin D3) stimulated PA activity in both cell types. The relative efficacies of vitamin D metabolites and of prostanoids reflect their relative potencies as stimulators of bone resorption.
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PMID:Stimulation of plasminogen activator in osteoblast-like cells by bone-resorbing hormones. 661 Nov 56

A human osteosarcoma cell line, U-2 OS, cultured under serum-free conditions, was shown to produce a growth factor (osteosarcoma-derived growth factor, ODGF) for human-cultured glial cells, fibroblasts, and other cells. ODGF, collected from the spent medium of 2 OS cultures, was purified by a sequence involving heparin-Sepharose chromatography, hydrophobic chromatography, gel chromatography, and preparative gel electrophresis in SDS. Purified ODGF, at a concentration of 3 ng/ml, elicited a mitogenic response in human glial cells equivalent to 50% of that afforded by human serum at a final concentration of 1%. The preparation was estimated to be > 50% pure. The biological activity of ODGF resided in a cationic, relatively heat-resistant, reduction-susceptible protein with a molecular weight of 30,000 (by gel chromatography and SDS-gel electrophoresis). The electrophoretic behaviour of radioiodinated ODGF suggested that the protein was composed of two different polypeptide chains (about 13,000-14,00 and 16,000-17,000 daltons, respectively) linked via disulphide bonds. The molecular makeup of ODGF was thus similar to that of platelet-derived growth factor. 125I-ODGF could be precipitated by an antibody to platelet-derived growth factor, indicating that the two factors were immunologically related. Resemblance with platelet-derived growth factor was also indicated by the finding that the latter (but not, e.g., fibroblast growth factor or epidermal growth factor) competed with 125I-ODGF for binding to human-cultured glial cells.
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PMID:Chemical and biological properties of a growth factor from human-cultured osteosarcoma cells: resemblance with platelet-derived growth factor. 693

In studies of the regulation of parathyroid hormone (PTH) signal transduction, we observed that the peptide endothelin-1 (ET) added prior to PTH greatly increased the calcium transients elicited by PTH in UMR-106 osteosarcoma cells and mouse primary osteoblastic cells. Enhancement by ET also occurred in the presence of EGTA. The ETB receptor-specific agonist sarafotoxin 6c (S6c) likewise enhanced PTH-induced Ca2+ transients. Blocking the ETA receptor-mediated component of the ET signal with BQ123 failed to abolish enhancement of PTH responses by ET. The nonselective ETA/ETB receptor antagonist PD 142893 blocked both ET and S6c-induced enhancement of the PTH responses. Prostaglandin F1 alpha (PGF1 alpha) pretreatment also maximally potentiated PTH responses, whereas alpha-thrombin, epidermal growth factor (EGF), or prostaglandin E1 (PGE1) did not affect the PTH responses. Neither active phorbol ester nor forskolin mimicked the ET effect. The ET effect was not prevented by indomethacin, NG-mono-methylarginine, genistein, pertussis toxin, 4-aminopyridine, tetraethylammonium chloride, okadaic acid, or long-term treatment with phorbol-12,13-dibutyrate. ET pretreatment did not abolish the inhibition of PTH signals by PTH(3-34), although in ET-pretreated cells the suppression of the PTH signal by PTH(3-34) was not as great. ET pretreatment did not enhance the cAMP response to PTH; rather, there was a significant inhibition of the cAMP response. Thus, the calcium signal elicited by PTH is selectively modulated by activation of the ETB receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:EndothelinB receptor activation enhances parathyroid hormone-induced calcium signals in UMR-106 cells. 750 6

Studies have shown an increased risk for breast cancer in the mothers of children suffering from retinoblastoma and osteosarcoma, suggesting a role for the retinoblastoma susceptibility (Rb) gene product in breast cancer. We now show that estradiol decreases the expression of Rb at the level of protein and messenger RNA (mRNA) in estrogen-dependent breast cancer cell lines. Treatment of MCF-7 cells with 10(-9) M estradiol for 48 h resulted in a 70% decrease in the level of Rb protein. Ribonuclease protection assays showed a 50% decrease in the steady state levels of Rb mRNA by 12 h and a 70% decrease in Rb mRNA by 24 h. Treatment with estradiol had no effect on the rate of Rb gene transcription or on Rb mRNA stability, but resulted in an increase in the steady state level of Rb mRNA in the nucleus. The effect of estradiol was inhibited by 10(-7) M 4-hydroxytamoxifen. In the absence of estradiol, the antiestrogens 4-hydroxytamoxifen and ICI 164,384 increased Rb mRNA by 50% over that in estrogen-depleted conditions. Estradiol regulation of Rb mRNA also occurred in other estrogen-dependent breast cancer cell lines. Insulin-like growth factor I, insulin, progestins, and epidermal growth factor had no effect on Rb expression. In summary, these results show that estradiol specifically regulates the expression of the Rb susceptibility gene product in hormone-dependent breast cancer by a posttranscriptional mechanism that occurs in the nucleus. The results from this study suggest that the negative regulation of Rb expression by estradiol, rather than Rb loss or mutation, may play an important role in breast carcinogenesis.
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PMID:Regulation of retinoblastoma gene expression in hormone-dependent breast cancer. 758 21

Osteoblast-like cells, such as UMR 106 osteosarcoma cells, are known to be growth stimulated by growth factors such as EGF. In contrast, factors such as PTH and prostaglandin E2 inhibit their growth. The exact signal transduction mechanisms by which these latter factors act remain to be elucidated. Here we show that simultaneous treatment of UMR 106 cells with EGF and PTH-(1-34) resulted in a level of DNA synthesis intermediate between the levels of treatment with epidermal growth factor (EGF) and PTH alone. This correlated with the interference of PTH-(1-34) early in an EGF receptor-linked signal transduction pathway, i.e. the EGF-induced activation of p42 mitogen-activated protein (MAP) kinase. This effect was also found for prostaglandin E2, and could be potentiated by the phosphodiesterase inhibitor isobutyl-methylxanthine and mimicked by forskolin and 8-bromo-cAMP. There was a strict correlation between the lowest concentration of PTH-(1-34) required to enhance protein kinase A (PKA) activity and that required to inhibit MAP kinase activation, whereas saturating amounts of PTH-(3-34), a PTH analog unable to elevate PKA activity, had no effect. Lysophosphatidic acid- and 12-O-tetracanoylphorbol-13-acetate-induced MAP kinase activation were also inhibited by PTH-(1-34) and forskolin in these cells. Similar effects were seen on basic fibroblast growth factor-mediated MAP kinase activation in ROS 17/2.8 cells, indicating that this mechanism is a general feature of PTH in osteosarcoma cells. The inhibition of this mitogenic pathway through activation of PKA might play an important role in PTH-induced changes in proliferation and differentiation of osteoblasts.
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PMID:Parathyroid hormone inhibits mitogen-activated protein kinase activation in osteosarcoma cells via a protein kinase A-dependent pathway. 762 68

Sequence information for aspartyl beta-hydroxylase (AspH), which specifically hydroxylates one Asp or Asn residue in certain epidermal growth factor (EGF)-like domains of a number of proteins, is so far only described for bovine species. We have isolated a 4.3-kb cDNA encoding the human AspH (hAspH) by immunoscreening of a human osteosarcoma (MG63) cDNA library in lambda ZAP with an antiserum raised against membrane fractions of these cells. Northern blot analyses revealed two transcripts with lengths of 2.6 and 4.3 kb. The deduced amino acid (aa) sequence of this cDNA encodes a protein of 757 aa (85 kDa). Comparison with the deduced bovine AspH (bAspH) aa sequence showed striking differences in the N-terminal portion of this protein. In vitro transcription and translation in the presence of canine pancreas microsomes yielded a 56-kDa protein. Western blot analyses of membrane fractions from MG63 cells with AspH-specific antibodies revealed a protein of the same M(r). These results suggest a posttranslational cleavage of the catalytic C terminus in the lumen of the endoplasmic reticulum.
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PMID:Cloning and characterization of the human gene encoding aspartyl beta-hydroxylase. 782 14

Parathyroid hormone-related peptide (PTHrP) was originally isolated from tumors associated with the development of hypercalcemia in vivo. Analyses of PTHrP gene expression have demonstrated that PTHrP is also produced in a wide variety of normal fetal and adult nonneoplastic tissues. The results of recent experiments have demonstrated that PTHrP is a growth factor-regulated gene, and different molecular forms of synthetic PTHrP display variable activities in assays for growth factor-like properties in vitro. We have studied the growth factor-like activity of PTHrP in cells transfected with a human PTHrP (hPTHrP) expression vector. Transfected cell lines contained increased amounts of PTHrP mRNA transcripts as assessed by Northern blot analysis. The PTHrP mRNA transcripts were translated into immunoreactive hPTHrP as measured by radioimmunoassay, and conditioned medium from transfected cell lines stimulated cyclic AMP (cAMP) formation in ROS 17/2.8 osteosarcoma cells. The transforming growth factor-beta-like properties of hPTHrP-producing NRK 49F clones were examined using the large-colony transformation assay in soft agar. PTHrP-producing NRK 49F clones did not form large colonies in the presence of epidermal growth factor. In contrast, PTHrP-producing and wild-type NRK 49F cells formed large colonies in the presence of epidermal growth factor and transforming growth factor-beta. No effect on cell growth was observed in PTHrP-producing NRK 49F rat kidney fibroblasts or mouse NIH 3T3 fibroblasts. In contrast, RCB 2.2 osteoblast cells expressing the hPTHrP cDNA were growth inhibited. Incubation of wild-type RCB 2.2 cells with synthetic hPTHrP[1-34] (at concentrations of 1.0-10.0 nM) also produced growth inhibition. PTHrP increased cAMP formation in RCB 2.2 cells but not in NIH 3T3 or NRK 49F cells. Incubation of RCB 2.2 cells with dibutyryl cAMP was also associated with inhibition of cell growth. The results of these studies demonstrate that PTHrP may function as an autocrine growth inhibitor of specific cell types, possibly through a cAMP-dependent pathway.
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PMID:Growth factor-like properties of parathyroid hormone-related peptide in transfected rodent cell line. 831 5

Prostate tumor cells preferentially metastasize to bony sites and lymph nodes at a frequency in excess of that which would be predicted by random tumor cell dissemination. In order to determine whether chemoattractants in these organs promote organ-specific metastasis, we utilized human cell lines derived from and/or related to these organs as sources of potential chemoattractants. Secretory proteins derived from the cell lines MG-63 (osteosarcoma), SK-ES-1 (Ewing's sarcoma), and KG-1 (leukemia) stimulated chemomigration of the TSU-pr1 prostate tumor cells in a dose-dependent manner in Boyden chambers. In addition, secretory proteins from a human prostatic stromal cell line (hPS) and from the TSU-Pr1 prostate tumor cell line were also able to stimulate chemomigration of the TSU-pr1 cells through Boyden chambers. Since lymph nodes and bony sites represent organs of hematopoietic/lymphoid proliferation and activation, we undertook identification of specific cytokines present at these sites which may promote the chemomigration of prostate tumor cells. In this context, the cytokines interleukin-1 alpha, interleukin-2, interleukin-6, tumor necrosis factor-beta, transforming growth factor-beta, interferon alpha 2-a, and granulocyte-macrophage colony-stimulating factor did not stimulate chemomigration of the TSU-pr1 prostate tumor cell line. In contrast, the cytokine epidermal growth factor (EGF) stimulated chemomigration of the TSU-pr1 prostate tumor cells through the Boyden chambers in a dose-dependent manner. Western blot analysis of secretory proteins from the cell lines KG-1, SK-ES-1, MG-63, hPS, and TSU-pr1 identified EGF-immunoreactive proteins in all cases. In addition, EGF immunoreactivity was localized to the stroma of the human prostate, the osteogenic stroma of pelvic medullary bone, and the stroma within the capsule and trabeculae of pelvic lymph nodes. Hence, these results demonstrate that the cytokine EGF promotes the chemomigration of the TSU-pr1 prostate tumor cell line, and that EGF within the stroma of pelvic lymph nodes and medullary bone may act as a chemoattractant for prostate tumor cells, thereby facilitating the preferential formation of metastatic foci within these organs.
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PMID:Epidermal growth factor (EGF) promotes chemomigration of a human prostate tumor cell line, and EGF immunoreactive proteins are present at sites of metastasis in the stroma of lymph nodes and medullary bone. 854 75


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