Kinetics of calcitonin receptor internalization in lung cancer (BEN) and osteogenic sarcoma (UMR 106-06) cells

2009 ◽  
Vol 1 (3) ◽  
pp. 277-283 ◽  
Author(s):  
David M. Findlay ◽  
T. John Martin
Keyword(s):  
Lung Cancer ◽  
Osteogenic Sarcoma ◽  
Receptor Internalization ◽  
Calcitonin Receptor ◽  
Umr 106 ◽  
Kinetics Of

scholarly journals Effect of 1,25-dihydroxyvitamin D3 on cyclic AMP responses to hormones in clonal osteogenic sarcoma cells

1985 ◽  
Vol 231 (1) ◽  
pp. 11-17 ◽  
Author(s):  
M Kubota ◽  
K W Ng ◽  
T J Martin
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Biological Activities ◽  
Osteogenic Sarcoma ◽  
Intact Cells ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Sarcoma Cells ◽  
Umr 106 ◽  
Kinetics Of

The effect of 1,25-dihydroxyvitamin D3 on adenylate cyclase responsiveness was studied in the clonal osteogenic sarcoma cell line, UMR 106-06, which responds to several bone active hormones. 1,25-dihydroxyvitamin D3 treatment had no consistent effect on basal formation of cyclic AMP in intact cells, but the responses to parathyroid hormone, isoproterenol, prostaglandin E2, salmon calcitonin and the plant diterpene, forskolin, were all attenuated, by up to 90%. The effect of 1,25-dihydroxyvitamin D3 was dose-dependent, with half-maximal effectiveness at 0.1 nM, and required 48 h treatment of cells before it became apparent. The relative potencies of other vitamin D3 compounds correlated closely with their relative affinities for the 1,25-dihydroxyvitamin D3 receptor and their biological activities in other systems. 1,25-dihydroxyvitamin D3 treatment had no effect on the kinetics of labelled calcitonin binding to UMR 106-06 cells. Furthermore, the fact that such a range of hormones was affected made a receptor mediated mechanism unlikely. Nucleotide stimulatory (Ns) unit activity was assayed after 1,25-dihydroxyvitamin D3 treatment and found to be unchanged. Islet activating protein, an inhibitor of nucleotide inhibitory unit (Ni) activity, failed to modify the 1,25-dihydroxyvitamin D3 effect. Thus the effect of 1,25-dihydroxyvitamin D3 appeared to be exerted beyond hormone receptor and nucleotide regulatory components of the adenylate cyclase complex. It is concluded that 1,25-dihydroxyvitamin D3 attenuates adenylate cyclase response to hormones by a direct or indirect action on the catalytic component of adenylate cyclase.

Modulation of glucose transport by parathyroid hormone and insulin in UMR 106–01, a clonal rat osteogenic sarcoma cell line

1995 ◽  
Vol 14 (2) ◽  
pp. 263-275 ◽  
Author(s):  
D M Thomas ◽  
S D Rogers ◽  
M W Sleeman ◽  
G M Pasquini ◽  
F R Bringhurst ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cell Line ◽  
Glucose Transport ◽  
Transport System ◽  
Osteogenic Sarcoma ◽  
Regulatory Subunit ◽  
Sarcoma Cell ◽  
Sarcoma Cell Line ◽  
Glucose Transport System ◽  
Umr 106

ABSTRACT This study characterizes the actions of insulin and parathyroid hormone (PTH) on the glucose transport system in the rat osteogenic sarcoma cell line UMR 106–01, which expresses a number of features of the osteoblast phenotype. Using [1,2-3H]2-deoxyglucose (2-DOG) as a label, UMR 106–01 cells were shown to possess a glucose transport system which was enhanced by insulin. In contrast, PTH influenced glucose transport in a biphasic manner with a stimulatory effect at 1 h and a more potent inhibitory effect at 16 h on basal and insulin-stimulated 2-DOG transport. To explore the mechanism of PTH action, a direct agonist of cAMP-dependent protein kinase (PKA) was tested. 8-Bromo-cAMP had no acute stimulatory effect but inhibited basal and insulin-stimulated 2-DOG transport at 16 h. This result suggested that the prolonged, but not the acute, effect of PTH was mediated by the generation of cAMP. Further studies with the cell line UMR 4–7, a UMR 106–01 clone stably transfected with an inducible mutant inactive regulatory subunit of PKA, confirmed that the inhibitory but not the stimulatory effect of PTH was mediated by the PKA pathway. Northern blot data indicated that the prolonged inhibitory effects of PTH and 8-bromo-cAMP on glucose transport were likely to be mediated in part by reduction in the levels of GLUT1 (HepG2/brain glucose transporter) mRNA.

Effects of Parathyroid Hormone and Insulin on Proliferation in Osteogenic Sarcoma UMR-106-01 Cells

1998 ◽  
Vol 33 (2) ◽  
pp. 466
Author(s):  
Kyung Moon ◽  
Choon Sung Lee ◽  
Jae Suk Chang ◽  
Key Yong Kim ◽  
Seong Who Kim ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Osteogenic Sarcoma ◽  
Umr 106

scholarly journals Kinetics of binding, endocytosis, and recycling of EGF receptor mutants

1992 ◽  
Vol 117 (1) ◽  
pp. 203-212 ◽  
Author(s):  
S Felder ◽  
J LaVin ◽  
A Ullrich ◽  
J Schlessinger
Keyword(s):  
Point Mutation ◽  
Phorbol Ester ◽  
Egf Receptor ◽  
Receptor Internalization ◽  
Affinity Binding ◽  
High Affinity Binding ◽  
High Affinity ◽  
Low Concentrations ◽  
Internalization Rate ◽  
Kinetics Of

This report describes analysis of factors which regulate the binding of EGF to EGF receptor, receptor internalization, and receptor recycling. Three different methods were used to inhibit high-affinity EGF binding as measured at equilibrium: treatment of cells with an active phorbol ester (PMA), binding of a mAb directed against the EGF receptor (mAb108), and truncation of most of the cytoplasmic domain of the receptor. These treatments reduced the rate at which low concentrations of EGF bound to cells, but did not affect the rate of EGF dissociation. We conclude that high-affinity EGF binding on living cells results from a difference in the apparent on rate of EGF binding. We then used these conditions and cell lines to test for the rate of EGF internalization at different concentrations of EGF. We demonstrate that internalization of the EGF receptor is stimulated roughly 50-fold at saturating concentrations of EGF, but is stimulated an additional two- to threefold at low concentrations (less than 1 nM). Four treatments reduce the rate of internalization of low concentrations of EGF to the rate seen at saturating EGF concentrations. Phorbol ester treatment and mAb108 binding to "wild type" receptor reduce this rate (and reduce high-affinity binding). Point mutation at Lys721 (kinase negative EGF receptor) and point mutation at Thr654 (removing a major site of protein kinase C phosphorylation) reduce the internalization rate, without affecting high-affinity binding. We suggest that while EGF stimulates endocytosis for all receptors, high-affinity receptors bind and are internalized more quickly than low-affinity receptors. Tyrosine kinase activity and the Thr654 region appear necessary for this response.

scholarly journals Kinetics of Plasma cfDNA Predicts Clinical Response in Non-Small Cell Lung Cancer Patients

2020 ◽  
Author(s):  
Xiaorong Zhou ◽  
Chenchen Li ◽  
Zhao Zhang ◽  
Daniel Y. Li ◽  
Jinwei Du ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Prognostic Biomarker ◽  
Checkpoint Inhibitors ◽  
Tumor Burden ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Kinetics Of

AbstractBackgroundTyrosine Kinases Inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs, bevacizumab) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancer including non-small-cell lung cancer (NSCLC). Cell-free DNA (cfDNA) has been adapted as a convenient liquid biopsy that reflects characteristics of the status of both the primary and metastatic tumors, assisting in personalized medicine. This study aims to evaluate the utility of cfDNA as a prognostic biomarker and efficacy predictor of chemotherapy with or without these precision therapies in NSCLC patients.MethodsPeripheral cfDNA levels were quantified in 154 patients with NSCLC before (baseline) and after (post-chemotherapy) the first target cycle of chemotherapy. These patients were divided into four subgroups receiving chemotherapy only, chemotherapy plus TKIs, chemotherapy plus VEGFIs, and chemotherapy plus immune checkpoint inhibitors (ICIs), respectively. The correlations of cfDNA with tumor burden, clinical characteristics, progression-free survival (PFS), objective response ratio (ORR), and therapy regimens were analyzed.ResultsBaseline cfDNA, but not post-chemotherapy, positively correlates with tumor burden. cfDNA Ratio (post-chemotherapy/baseline) well distinguished responsive individuals (CR/PR) from non-responsive patients (PD/SD). Additionally, cfDNA Ratio was found to be negatively correlated with PFS in lung adenocarcinoma (LUAD), but not in lung squamous-cell carcinoma (LUSC). LUAD patients with low cfDNA Ratio benefit significantly including prolonged PFS and improved ORR, compared with those with high cfDNA Ratio. When stratified by therapy regimen, the predictive value of cfDNA Ratio is significant in patients with chemotherapy plus VEGFIs.ConclusionThe kinetics of plasma cfDNA during the chemotherapy may function as a prognostic biomarker and efficacy predictor for NSCLC patients.

Newly synthesized glycoconjugates from two cell lines derived from rat osteogenic sarcoma: effects of Matrigenin activity from bone

1991 ◽  
Vol 69 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Ravi K. Chopra ◽  
Tassos Anastassiades ◽  
Christian Stephens ◽  
David Lohnes ◽  
Glenville Jones
Keyword(s):  
Cell Lines ◽  
Osteogenic Sarcoma ◽  
Distinct Species ◽  
Enzymatic Digestion ◽  
Proteoglycan Synthesis ◽  
Tissue Cell ◽  
Osteoblastic Cell ◽  
Bovine Bone ◽  
The Media ◽  
Umr 106

An activity isolated from bovine bone was previously shown to stimulate proteoglycan synthesis by several connective tissue cell lines from normal tissues (Matrigenin activity). The effect of this activity on glycoconjugate synthesis by two osteoblastic cell lines, ROS 17/2 and UMR-106, derived from rat osteogenic sarcoma, was examined after labelling of the cells with [3H]glucosamine and [35S]sulfate. The glycoconjugates from the cell layers and the media were separated by DEAE-Sephacel chromatography and the anionic glycoconjugates of the media were further analyzed by chromatography on Sepharose CL-2B and enzymatic digestion of the papain-released glycosaminoglycans. The ROS 17/2 cells secreted at least two distinct species of proteoglycan (one heparan sulfate rich and the other chondroitin sulfate rich), whereas the UMR-106 secreted primarily an anionic glycoprotein. The addition of Matrigenin activity to the ROS 17/2 cells resulted in stimulation of incorporation of radioactivity into the proteoglycan and hyaluronic acid, but in UMR-106 cultures it resulted in decreased incorporation into the anionic glycoprotein. The decrease in incorporation into the anionic glycoprotein from the medium was shown, by alkaline β-elimination, to have occurred mainly in the oligosaccharide fraction, relative to control cultures.Key words: osteogenic sarcoma cells, Matrigenin activity, glycoconjugate synthesis.

scholarly journals The p53–53BP1-Related Survival of A549 and H1299 Human Lung Cancer Cells after Multifractionated Radiotherapy Demonstrated Different Response to Additional Acute X-ray Exposure

2020 ◽  
Vol 21 (9) ◽  
pp. 3342
Author(s):  
Margarita Pustovalova ◽  
Lina Alhaddad ◽  
Nadezhda Smetanina ◽  
Anna Chigasova ◽  
Taisia Blokhina ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Strand Break ◽  
Human Lung Cancer ◽  
Cancer Resistance ◽  
Cellular Mechanisms ◽  
X Ray ◽  
Γh2ax Foci ◽  
Therapeutic Benefits ◽  
Different Response ◽  
Kinetics Of

Radiation therapy is one of the main methods of treating patients with non-small cell lung cancer (NSCLC). However, the resistance of tumor cells to exposure remains the main factor that limits successful therapeutic outcome. To study the molecular/cellular mechanisms of increased resistance of NSCLC to ionizing radiation (IR) exposure, we compared A549 (p53 wild-type) and H1299 (p53-deficient) cells, the two NSCLC cell lines. Using fractionated X-ray irradiation of these cells at a total dose of 60 Gy, we obtained the survived populations and named them A549IR and H1299IR, respectively. Further characterization of these cells showed multiple alterations compared to parental NSCLC cells. The additional 2 Gy exposure led to significant changes in the kinetics of γH2AX and phosphorylated ataxia telangiectasia mutated (pATM) foci numbers in A549IR and H1299IR compared to parental NSCLC cells. Whereas A549, A549IR, and H1299 cells demonstrated clear two-component kinetics of DNA double-strand break (DSB) repair, H1299IR showed slower kinetics of γH2AX foci disappearance with the presence of around 50% of the foci 8 h post-IR. The character of H2AX phosphorylation in these cells was pATM-independent. A decrease of residual γH2AX/53BP1 foci number was observed in both A549IR and H1299IR compared to parental cells post-IR at extra doses of 2, 4, and 6 Gy. This process was accompanied with the changes in the proliferation, cell cycle, apoptosis, and the expression of ATP-binding cassette sub-family G member 2 (ABCG2, also designated as CDw338 and the breast cancer resistance protein (BCRP)) protein. Our study provides strong evidence that different DNA repair mechanisms are activated by multifraction radiotherapy (MFR), as well as single-dose IR, and that the enhanced cellular survival after MFR is reliant on both p53 and 53BP1 signaling along with non-homologous end-joining (NHEJ). Our results are of clinical significance as they can guide the choice of the most effective IR regimen by analyzing the expression status of the p53–53BP1 pathway in tumors and thereby maximize therapeutic benefits for the patients while minimizing collateral damage to normal tissue.

scholarly journals Effect of parathyroid hormone on phospholipid metabolism in osteoblast-like rat osteogenic sarcoma cells

1986 ◽  
Vol 236 (2) ◽  
pp. 605-608 ◽  
Author(s):  
T Matsumoto ◽  
K Morita ◽  
Y Kawanobe ◽  
E Ogata
Keyword(s):  
Parathyroid Hormone ◽  
Osteogenic Sarcoma ◽  
Phospholipid Metabolism ◽  
Time Dependent ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Maximal Dose ◽  
Sarcoma Cells ◽  
Umr 106 ◽  
Stimulation Of

Previous results have shown that 1,25-dihydroxycholecalciferol [1,25(OH)2D3] enhances the synthesis of phosphatidylserine (PS) and suppresses the synthesis of phosphatidylethanolamine (PE) in osteoblast-like rat osteogenic sarcoma UMR 106 cells [Matsumoto, Kawanobe, Morita & Ogata (1985) J. Biol. Chem. 260, 13704-13709]. In the present study, the effect of parathyroid hormone (PTH) on phospholipid metabolism is examined by using these cells. Treatment of UMR 106 cells with human PTH-(1-34)-peptide suppresses the synthesis of phosphatidylethanolamine in a dose- and time-dependent manner without affecting the synthesis of PS. The maximal effect on PE synthesis is obtained with 2.4 nM-human PTH-(1-34)-peptide when the cells are treated for 48 h or longer. In addition, when human PTH-(1-34)-peptide is added together with the maximal dose of 1,25(OH)2D3, there is a further decline in PE synthesis, whereas the stimulation of PS synthesis by 1,25(OH)2D3 is not altered. Because methylation of PE is suggested to affect hormone receptor-adenylate cyclase coupling, the observed change in PE metabolism by PTH and 1,25(OH)2D3 may be, at least in part, involved in the development of desensitization phenomenon to PTH in these cells.

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