Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00369 (ROS)
 19,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Confluent cultures of rat bone cells synthesize several forms of secreted phosphoprotein 1 (SPP-1, osteopontin), the major phosphorylated forms of which migrate at 55 and 44 kDa on 15% cross-linked SDS-PAGE gels and correspond to the transformation-associated proteins pp 69 and pp 62. A clonal rat calvarial cell line (RCA 11), which expressed the highest level of SPP-1, produced only the 55 kDa form of the phosphorylated protein, whereas normal rat calvarial cells enriched in osteoblastic cells (RC IV cells) produced mostly the 55 kDa form, with small amounts of the 44 kDa form. In contrast, a 44 kDa form was the major [32PO4]-labelled SPP-1 synthesized by a rat osteocarcoma cell line (ROS 17/2.8 cells) with lesser amounts of the 55 kDa SPP-1. When [35S]methionine was used to measure protein synthesis, only the 55 kDa SPP-1 could be clearly detected in confluent cultures of each cell population, indicating that the 55 kDa SPP-1 is the prominent form of SPP-1 synthesized by each cell population. Following treatment of the normal rat bone cells for 24 h with osteotropic hormones (vit D3, PTH and RA), growth factors (PDGF, EGF, TGF-beta), a tumor promoter (TPA) and a plant lectin (Con A), the 55 kDa [35S]methionine labelled SPP-1 was increased 1.7-8.3-fold. Similar, but generally lower responses were observed in the clonal RCA 11 cell line, whereas the ROS 17/2.8 cells were more refractory, showing only a strong response to vit D3. In general, vit D3 produced the strongest stimulation in all populations with TGF-beta producing a good response in the non-transformed cells and RA in the RC IV cells. In contrast, PTH was inhibitory in both RCA 11 and ROS 17/2.8 cells. In most, but not all, cases the alteration in SPP-1 synthesis reflected similar changes in SPP-1 mRNA and in the intensity of the [32PO4]-labelled 55 kDa SPP-1. Collectively, these studies demonstrate that bone cells produce several forms of SPP-1 which are differentially regulated in normal and transformed cells through both transcriptional and posttranscriptional mechanisms.
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PMID:Differential regulation of the 55 and 44 kDa forms of secreted phosphoprotein 1 (SPP-1, osteopontin) in normal and transformed rat bone cells by osteotropic hormones, growth factors and a tumor promoter. 186 11

Recent efforts have been directed at identifying and characterizing candidate tumor suppressor genes and the activities of oncogenes in primary brain tumors. The p53 gene mapping to region p13 of chromosome 17 has several characteristics as a tumor suppressor gene. The wild-type p53 protein, which is a transcriptional activator, may serve as a barrier to the progression of neoplastic processes, and alterations of p53 are involved in genesis of various cancers including astrocytomas. The NF1 gene, which is responsible for the susceptibility to neurofibromatosis type 1, has recently been isolated. This gene is assumed to play a role in the signal transduction pathway by interacting with the ras gene product. Recent observation revealed that the NF1 gene may regulate the neuronal differentiation, and the alteration in regulation of the NF1 transcript is potentially related to the progression of neuroectodermal tumors. Restriction fragment length polymorphism studies have also shown chromosomal losses associated with chromosome 9, 10 and 17. These losses of genetic material are suspected to involve loci near or at the p53 gene for chromosome 17, and neighboring the interferon genes on chromosome 9. Although no sublocalization of chromosome 10 deletions has been accomplished, all of these loci are thought to harbor tumor suppressor genes. Recent advances in oncogene research have focused on understanding the mechanisms of action of growth factors, growth factor receptors, and their substrates, particularly in glial oncogenesis. Fibroblast growth factor, epidermal growth factor, and their respective receptors are of particular interest. However, the ROS oncogene, which is expressed and rearranged in some glioma cell lines, may not be a critical factor in the development of gliomas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathways of oncogenesis in primary brain tumors. 190

Twigs-dry leaves smoke condensate (TDS), as a source of clastogenic ROS and carcinogenic PAH, was investigated for its in vitro DNA-damaging effect in calf thymus DNA and human peripheral lymphocytes. An aqueous turmeric component--Aq.T--with an established antioxidant activity, was tested as a DNA protectant. TDS induced 13-fold damage to calf thymus DNA as judged by the emergence of a DNA damage specific, fluorescent product (em: 405 nm). Aq.T at 800 ng/microL extended 69% protection to calf thymus DNA and was comparable to the other protectants such as curcumin, BHA, vitamin E, SOD, and CAT. In human peripheral lymphocytes, TDS induced extensive DNA damage in comparison with the tumor promoter TPA, as judged by FADU. Aq.T at 300 ng/microL extended 90% protection to human lymphocyte DNA against TDS-induced damage, and was more effective than the other protectants--DABCO, D-mannitol, sodium benzoate, vitamin E (ROS quenchers), SOD, CAT (antioxidant enzymes), tannic acid, flufenamic acid, BHA, BHT, n-PG, curcumin and quercetin (antioxidants). Aq.T offered 65% protection to human lymphocyte DNA against TPA-induced damage and was comparable to SOD. The above results indicate that TDS induces substantial DNA damage in calf thymus DNA and human lymphocytes and Aq.T is an efficient protectant.
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PMID:DNA damage by smoke: protection by turmeric and other inhibitors of ROS. 193 45

PTH-related peptide (PTHrP) may be a major cause of the humoral hypercalcemia of malignancy. The circulating form of PTHrP is unknown, but mRNA analysis of tumor tissue suggests that multiple forms of PTHrP may exist. Therefore, we examined the ability of the full 141-amino acid protein as well as 2 amino-terminal fragments, PTHrP-(1-34) and PTHrP-(1-74), to increase cytosolic calcium ion concentrations ([Ca2+]i; assessed by aequorin luminescence) and stimulate cAMP accumulation in osteoblast-like rat osteosarcoma cells (ROS 17/2.8). PTH and all PTH-related peptides examined increased [Ca2+]i and cAMP in a concentration-dependent manner. The [Ca2+]i response to PTHrP-(1-34) closely resembled that to rat PTH-(1-34); both peptides produced biphasic responses. However, the responses to the longer PTHrP fragments generally were not biphasic. There were no significant differences among the three PTHrP forms in increasing [Ca2+]i or stimulating cAMP accumulation, although PTHrP-(1-74) was consistently weaker than the other two PTHrP peptides. PTHrP-(1-34) was more potent than rPTH-(1-34), which, in turn, was more potent than human PTH-(1-34) in increasing [Ca2+]i. However, PTHrP-(1-34) was not consistently more potent than either human PTH-(1-34) or rat PTH-(1-34) in stimulating cAMP accumulation. The inhibitory PTH analog bovine PTH-(3-34) attenuated both cAMP and [Ca2+]i responses to PTHrP-(1-34), but bovine PTH-(7-34) only reduced the [Ca2+]i response. Our data are generally consistent with PTHrP's acting through the PTH receptor, but differences in the effects of inhibitory PTH analogs on PTH and PTHrP action suggest as yet unexplained complexities, such as the existence of a PTH/PTHrP receptor family.
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PMID:Structure-function relationships for full-length recombinant parathyroid hormone-related peptide and its amino-terminal fragments: effects on cytosolic calcium ion mobilization and adenylate cyclase activation in rat osteoblast-like cells. 230 14

Both parathyroid hormone (PTH)- and forskolin-stimulated adenylate cyclase activities in ROS 17/2.8 cells are enhanced by increasing the medium concentrations of CaCl2 from 10(-5) M to 3 x 10(-3) M. The ED50 for CaCl2 for both PTH- and forskolin-stimulated activities are similar. The tumor-promoting phorbol ester phorbol 12-myristate 13-acetate (PMA), a known activator of protein kinase C, also enhanced both PTH- and forskolin-stimulated adenylate cyclase. This action of PMA is specific for protein kinase C as phorbol esters that are not activators of protein kinase C had no effect on the system. The combined effects of PMA and CaCl2 were more than additive. The separate and combined effects of PMA and CaCl2 changed the rate of activation of the enzyme (Vmax) but did not modify the ED50 for PTH or for forskolin. PMA and CaCl2 both enhanced the potentiating effect of submaximal dose of forskolin on PTH-stimulated adenylate cyclase. It is concluded that calcium and PMA enhance PTH-sensitive adenylate cyclase and increase the production of cAMP by a mechanism that appears to involve the catalytic subunit of the enzyme and probably its interaction with a guanine nucleotide regulatory protein.
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PMID:Calcium and protein kinase C enhance parathyroid hormone- and forskolin-stimulated adenylate cyclase in ROS 17/2.8 cells. 250 26

We examined the osteoblastic phenotype of permanently transfected ROS 17/2.8 cells in culture and in vivo, in order to evaluate their relevance for studies of the regulation of gene expression and gene function in osteoblastic cells. Recent reports indicate that the progeny transfected cells may substantially vary and differ from the parental cell line in their phenotype, particularly in their tumorigenicity. ROS 17/2.8 cells were transfected with genetic constructs expressing the CAT gene from either the rat alpha 1 (I) or the mouse alpha 2 (I) collagen promoters. Forty-four clonal cell lines display a range of CAT expression from the transfected collagen promoters in culture. Four of these cell lines were further characterized. Alkaline phosphatase activity in these four cell lines is higher than in fibroblastic cells. These four cell lines are tumorigenic in immunocompatible ACI rats and form calcified tumors similar to those formed by ROS 17/2.8. CAT expression could be demonstrated in tumor extracts of two of the four cell lines, which also expressed higher CAT levels in culture. We conclude that permanently transfected ROS 17/2.8 derived cell lines maintain their tumorigenicity and their osteoblastic-like phenotype, and thus may provide a useful system for studies of gene function and regulation in osteoblast-like cells and bone-like tissue in vivo.
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PMID:Expression of chloramphenicol acetyltransferase (CAT) from rodent type I collagen promoters in transfected osteosarcoma cells in vivo. 255 4

A patient with peripheral T-cell Lymphoma and acquired, systemic osteosclerosis is described. Bone histology showed a spectacular activation of osteoblasts accompanyed by massive new bone formation. Alkaline phosphatase in serum was elevated and increased to greater than 2000 U/l when the lymphoma became refractory to chemotherapy. In the patient's serum an osteoblast-activating factor could be demonstrated using a rat osteogenic osteosarcoma cell line (ROS 17/2.8). The factor was absent during remission of the tumor. We conclude that osteosclerosis was a paraneoplastic syndrome in this patient due to the secretion of an osteoblast-stimulating factor by the T-cell lymphoma. This situation is similar to the secretion of osteoclast-activating factors described in B-cell lymphomas, particularly multiple myeloma. The characterization of such a factor could be of therapeutic relevance.
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PMID:Evidence for an osteoblast-activating factor in a patient with peripheral T-cell lymphoma and osteosclerosis. 278 45

A new cell line, designated EC-GI, was established from a 65-year-old patient with esophageal carcinoma who developed humoral hypercalcemia. The original tumor as well as the cell line caused marked hypercalcemia in tumor-bearing nude mice, in which a marked increase in osteoclastic bone resorption was demonstrated. The conditioned medium of EC-GI cells contained potent bone resorbing activity which stimulated cyclic AMP production in parathyroid hormone (PTH)-responsive osteoblast-like cells (ROS 17/2.8). EC-GI cells will be useful for characterization and purification of the PTH-like factor responsible for humoral hypercalcemia of malignancy.
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PMID:Establishment of a parathyroid hormone-like factor-producing esophageal carcinoma cell line (EC-GI). 282 16

A tumor-derived factor believed to cause hypercalcemia by acting on the parathyroid hormone (PTH) receptor was recently purified, cloned, and found to have NH2-terminal sequence homology with PTH. The 1-34 region of this protein was synthesized, evaluated for its postreceptor effects on the ROS 17/2.8 cell line, and its properties were compared to 1-34 PTH. Both 1-34 human humoral hypercalcemia factor (HCF) and 1-34 PTH stimulated adenylate cyclase with an effective concentration (EC)50 of approximately 1 nM. The extent of stimulation by both peptides was equally enhanced by dexamethasone. They both had a pronounced inhibitory effect on growth in the presence of dexamethasone, with an EC50 of approximately 0.1 nM, reduced alkaline phosphatase (AP) activity by approximately 70% in the absence of dexamethasone and by approximately 80% in the presence of dexamethasone with an EC50 of 0.03 nM, and when present at a concentration of 10 nM, reduced AP mRNA levels (estimated by Northern analysis) by approximately 80% in the presence or absence of dexamethasone. Thus, in addition to similar dose-response curves for adenylate cyclase stimulation, both HCF and PTH produced identical postreceptor effects in ROS 17/2.8 cells. These effects of HCF are probably mediated by the interaction of the tumor-derived factor with the PTH receptor.
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PMID:Comparison of postreceptor effects of 1-34 human hypercalcemia factor and 1-34 human parathyroid hormone in rat osteosarcoma cells. 283 Mar 17

[Tyr36]human adenylate cyclase stimulating peptide (1-36)-NH2, an amino-terminal analog of a tumor peptide which is associated with hypercalcemia of malignancy, and [Nle8, Nle18, Tyr34]bovine parathyroid hormone (PTH)-(1-34)-NH2 both bind with similar affinities to receptors on rat osteosarcoma cells, ROS 17/2.8, when either of the peptides is used as the radioligand. Pretreatment of the cells with either peptide down-regulates available binding sites for either radioligand and desensitizes the cAMP accumulation stimulated by either peptide. Prior exposure of the cells to dexamethasone increases these responses to both peptides. Photoderivatized radioiodinated [Tyr36]human adenylate cyclase-stimulating peptide (1-36)-NH2 and [Nle8, Nle18, Tyr34]bovine PTH-(1-34)-NH2 both specifically label a Mr = 80,000 membrane protein on ROS 17/2.8 cells. The intensity of labeling this receptor band by either photoprobe is reduced by co-incubation with either peptide over the same dose range. Equivalent dose-dependent down-regulation of receptors which bind both photoprobes is also found when ROS 17/2.8 cells are preincubated with either peptide. Dexamethasone increases the intensity of receptor labeling. Our findings strongly indicate that both peptides recognize the same plasma membrane receptor on ROS 17/2.8 cells. Although the physiological function(s) of human adenylate cyclase-stimulating peptide is unknown, these results could explain why its biological actions on mineral ion metabolism so closely simulate those of PTH and raise interesting questions about the general biological and evolutionary significance of the use of the same receptor by chemically distinct peptides.
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PMID:The parathyroid hormone-like peptide associated with humoral hypercalcemia of malignancy and parathyroid hormone bind to the same receptor on the plasma membrane of ROS 17/2.8 cells. 283 57


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