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)

Cyclic AMP production by freshly isolated cells, from a 32P-induced transplantable rat osteogenic sarcoma, was stimulated by PGE1, PGE2 and to a less extent by PGF2alpha and PGA2. In the case of PGE2, the cyclic AMP content of cells was maximal within 5 min. The 13,14-dihydroderivatives of PGE1, PGE2 and PGF2alpha had approximately 40% of the activity of the parent prostaglandin whilst, in every case, the metabolites (15-keto and 13,14-dihydro-15-keto) had very little activity. Two prostaglandin endoperoxide analogues (U44069 and U46619) had only 10% of the activity of an equimolar dose of PGE2. The data presented in this paper demonstrates similarities between the responses of these cells and cells derived from bony tissue in terms of the ability of prostaglandins to stimulate bone resorption in tissue culture.
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PMID:Rat osteogenic sarcoma cells:effects of some prostaglandins, their metabolites and analogues on cyclic AMP production. 19 86

Adenylate cyclase activity in particulate fractions from a transplantable rat osteogenic sarcoma was stimulated in a dose-dependent manner by prostaglandins E1 and E2 (PGE1 and PGE2) and parathyroid hormone (PTH). Prostaglandin F2alpha was active at a high concentration (3 x 10(-4) mol/l). Pretreatment of membranes with collagenase plus hyaluronidase reduced the magnitude of the PTH effect but did not affect the size of the PGE1 effect. Guanosine 5'-triphosphate and its synthetic analogue 5'-guanylylimidodiphosphate (Gpp(NH)p) activated adenylate cyclase in particulate preparations from the osteogenic sarcoma. The latter agent produced much larger effects, although the concentrations required for half-maximal enzyme activation were the same for both agonists (approximately 2 x 10(-6) mol/l). The effects of PTH and Gpp(NH)p were supra-additive at some concentrations of hormone. The effects of PGE1 and Gpp(NH)p were supra-additive at all hormone concentrations tested. Pre-incubation of membrane particles for 6 min with PTH produced an enzyme activation which was not reversed by dilution through washing; pre-incubation with PGE1 did not produce this effect. The response of membrane adenylate cyclase to Gpp(NH)p (10(-4) mol/l) was 75% greater in preparations pre-incubated with PTH than in membranes pre-incubated in buffer alone or in buffer containing PGE1. The basal rate of cyclic AMP production in the adenylate cyclase assay system decreased over a 35 min incubation period. This decrease was prevented by addition of PTH or PGE1. Addition of NaF or Gpp(NH)p produced a steady increase in the rate of production of cyclic AMP with time. Membrane preparations did not reduce the biological activity of PTH and did not degrade 125I-labelled PTH. The results demonstrate that the PTH- and PGE-responsive adenylate cyclases of the osteogenic sarcoma have distinctly different properties and that particulate preparations of the tumour do not metabolize PTH.
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PMID:Membranes from a transplantable osteogenic sarcoma responsive to parathyroid hormone and prostaglandins: regulation of adenylate cyclase and of hormone metabolism. 27 36

Some human tumor cell lines express the c-sis gene, the proto-oncogene of the transforming gene v-sis, and produce platelet-derived growth factor, which may contribute to carcinogenesis by autocrine or paracrine mechanisms. Here we demonstrate that c-sis expression in some human glioma and osteosarcoma cell lines can be blocked by agents that increase cellular cyclic adenosine monophosphate (cAMP). Forskolin, 8-bromocyclic AMP, cholera toxin, and prostaglandin E1 reduced c-sis mRNA in these cells by up to 90%. c-sis transcription rates were reduced by agents that increase cAMP; the stability of c-sis mRNA was unaffected. The possible therapeutic value of blocking the expression of tumor growth factor genes pharmacologically warrants further study.
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PMID:Cyclic AMP blocks expression of the c-sis gene in tumor cells. 254 92

A wide spectrum of prostaglandins (PG) stimulate both the production of cyclic AMP and an increase in free cytosolic Ca2+ concentration [( Ca2+]i) in the osteogenic osteosarcoma cell line, UMR-106-01, which has characteristics compatible with osteoblasts. Using PG-stimulated determinations of the second messengers cyclic AMP and [Ca2+]i, a method for classification of PG receptors is presented. UMR-106-01 cells demonstrate three subclasses of PG receptors. One receptor interacts with PGF2 alpha, PGD2, and thromboxane B2 (TxB2) to increase [Ca2+]i. A second receptor binds PGE2, PGE1, PGI2, PGA2 and 6-oxo-PGF1 alpha to increase [Ca2+]i by stimulation of a second separate phospholipase C pool. A third receptor accepts PGE2, PGE1, PGA2, PGI2 and to a lesser extent PGF2 alpha, PGD2 and TxB2 to increase cyclic AMP. Such a classification system may be applicable to other cells responding to multiple PGs by inducing changes in cellular second messengers.
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PMID:Classification of prostaglandin receptors based on coupling to signal transduction systems. 255 9

The effects of interleukin 1, transforming growth factor-beta (coupling factors), prostaglandin E1, and prostaglandin E2 on incorporation of 45Ca2+ and on alkaline phosphatase activity were studied using cultured ROS 17/2.8 cells, one of cell lines derived from rat osteosarcoma. We found that all these factors stimulate both the incorporation of 45Ca2+ and alkaline phosphatase activity of these cells. On the other hand, one of the bone resorption hormones, parathyroid hormone (PTH), suppressed the proliferation of cells and decreased the alkaline phosphatase activity at considerably low concentrations (1 X 10(-12)-1 X 10(-11) M). However, the hormone stimulated the incorporation of 45Ca2+ by these cells in a dose-dependent manner; the maximum stimulation on day 3 was observed at 1 X 10(-7) M and it was approximately 3 times the control value. The data suggest therefore, that the osteoblasts incorporated calcium ions and transported them while bone resorption was occurring. Thus the ROS 17/2.8 cell line appears to be an advantageous experimental system for the study of calcium metabolism of osteoblasts in vitro.
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PMID:[Effects of various factors involved in bone metabolism on 45Ca2+ incorporation and alkaline phosphatase activity of ROS 17/2.8 cells]. 260 4

Human renal carcinoma cell line 786-0 elaborates a protein that is structurally and immunochemically distinct from parathyroid hormone (PTH) and that activates renal cortical adenylate cyclase via an interaction with the PTH receptor. Because of the high frequency of excessive bone resorption and resultant hypercalcemia in patients with malignant disease we evaluated the ability of this 786-0 cell factor to reproduce PTH action in bone-derived cells. The 786-0 factor as well as bovine PTH (BPTH) (1-34) and prostaglandin E1 produced marked increases in cyclic adenosine 3':5'-monophosphate (cAMP) accumulation in the clonal rat osteosarcoma cell line UMR-106. A competitive antagonist of PTH action, [norleucine8, norleucine18, tyrosine34] BPTH(3-34)amide, blocked the cAMP stimulation produced by 786-0 factor and BPTH(1-34) but not that produced by prostaglandin E1. In the presence of forskolin (0.1 microM) UMR-106 cells were extremely sensitive to 786-0 factor, showing significant increases in cAMP production at a concentration 10-fold less than that required to activate adenylate cyclase in renal membranes. In contrast UMR-106 cells were less sensitive to BPTH(1-34) than were renal membranes. This preferential increase in sensitivity to 786-0 factor was not seen in membranes prepared from UMR-106 cells suggesting the importance of cytosolic components. Six additional human genitourinary carcinoma cell lines were found to produce factors that increased cAMP levels in UMR-106 cells. We conclude that 786-0 factor is a potent activator of the PTH receptor-adenylate cyclase system in these bone-derived cells. These findings are consistent with the view that cancer-associated hypercalcemia may frequently be attributable to tumor secretion of proteins (such as 786-0 factor) that are distinct from PTH but are capable of activating skeletal PTH receptors.
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PMID:Activation of the parathyroid hormone receptor-adenylate cyclase system in osteosarcoma cells by a human renal carcinoma factor. 299 59

L-ascorbic acid at physiological concentrations (10 micrograms/ml) increased alkaline phosphatase activity in the osteoblastlike rat osteosarcoma cell line, UMR-106. The increase was dose-dependent and detectable at 6 hours after the addition of 100 micrograms/ml ascorbic acid to the medium. Treatment of the cells with 100 micrograms/ml ascorbic acid potentiated the response of cAMP to both PTH and PGE1, while cell growth was inhibited. Furthermore, the number of colonies formed by the cells grown in the soft agar was significantly reduced by increasing concentrations of ascorbic acid. These results indicate that ascorbic acid might play some role in the differentiation of osteoblasts.
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PMID:Effects of ascorbic acid on alkaline phosphatase activity and hormone responsiveness in the osteoblastic osteosarcoma cell line UMR-106. 301 92

Using tumour cell lines derived from human bone tumours, specific binding sites for epidermal growth factor (EGF), a potent growth stimulator in many tissues, and its effect on synthesis of prostaglandin (PG) E2, a potent bone-resorbing factor, by cultured osteosarcoma cell line were studied. Three tumour cell lines, one osteosarcoma (HOSO) and two giant cell tumours of the bone (G-1 and G-2), all possessed specific binding sites for 125I-labelled EGF: the apparent dissociation constant was approximately 4-10 X 10(-10) M and the maximal binding capacity was 50 000-80 000 sites/cell. EGF had no mitogenic effect in these cell lines. However, these cell lines did not have specific binding sites for 125I-labelled parathyroid hormone (PTH) or calcitonin. HOSO line produced and secreted PGE2 into medium, while no significant amount of PGE2 was demonstrated in G-1 or G-2 line. EGF significantly stimulated PGE2 production in HOSO line in a dose-dependent manner (0.5-50 ng/ml); its stimulatory effect was completely abolished by indomethacin, an inhibitor of PG biosynthesis. Exogenous PGE1 significantly stimulated cyclic AMP formation in HOSO line, whereas PGF2 alpha, PTH, calcitonin, or EGF had no effect. None of these calcium-regulating hormones affected cyclic AMP generation in either G-1 or G-2 line. These data indicate that human bone tumour cells have specific EGF receptors unrelated to cell growth, and suggest that EGF may be involved in bone resorption through a PGE2-mediated process in human osseous tissues.
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PMID:Specific receptors for epidermal growth factor in human bone tumour cells and its effect on synthesis of prostaglandin E2 by cultured osteosarcoma cell line. 609 85

Prostaglandin E (PGE) stimulates resorption in bone. Since osteoblast-like osteosarcoma cells secrete PGE2, the possibility that osteoclasts were the major target for PGE was considered. To study this question, it was first established that in isolated bone cells enriched for either osteoclastic (OC) or osteoblastic (OB) characteristics, PGE1 can induce biochemical effects similar to those seen with bovine parathyroid hormone 1-84 (PTH), another potent stimulator of bone resorption. These changes include increased cAMP and hyaluronate synthesis in OC cells, and increased cAMP but decreased citrate decarboxylation in OB cells. By following these markers, it is demonstrated that PGE1 can activate OC cells at doses as low as 1 nM, whereas OB cells require 250 nM. Bone cell responses to various doses of PTH and PGE1 were also compared. In OC cells the lowest effective dose of PGE1 and PTH was similar (1 nM), but increasing response to PGE1 was seen up to 1000 nM in contrast to PTH response which peaked at 20 nM. In addition, the magnitude of PGE1-induced OC cell hyaluronate was two to four times greater than that of PTH at all doses tested. In OB cells, PTH induced significant decreases in citrate decarboxylation at 0.1 nM, compared to 250 nM for PGE1. Half-maximal inhibition of citrate decarboxylation (19% of control) by PTH occurred at 0.5 nM, whereas 500 nM of PGE1 was required for an equivalent effect. Thus, (i) OC cells responded to PGE1 doses that were approximately 200 times lower than the minimum required by OB cells, and (ii) OB cells responded to 100 times lower doses of PTH than PGE1.
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PMID:Differential sensitivity of osteoclasts and osteoblasts suggests that prostaglandin E1 effects on bone may be mediated primarily through the osteoclasts. 630 50

The cytotoxic effect of prostaglandin (PG) D2, PGE1 and PGF2 alpha was examined on human osteosarcoma cells (KSu cell line) in vitro, and PGD2 was most effective. DNA, RNA and protein syntheses of KSu cells were also found to be inhibited by PGD2 at a concentration of 5 micrograms/ml. Furthermore, the proliferation of various human malignant tumor cells was inhibited by PGD2 without exception so far. These results suggest that PGD2 shows an anti-neoplastic effect on a variety of human malignant tumor cells.
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PMID:Prostaglandin D2 inhibits the proliferation of human malignant tumor cells. 658 41


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