Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Simian virus 40 (SV40) large tumor antigen (T) is an oncoprotein whose biological and biochemical functions appear to be modulated by phosphorylation. Recently, SV40 DNA replication in vitro has been shown to be activated by dephosphorylation involving the activity of a serine/threonine phosphoprotein phosphatase belonging to the type 2A class (PP2A) [Virshup, D.M., Kauffman, M.G. & Kelly, T.J. (1989) EMBO J., 8, 3891-3898]. To address the question of how specificity of PP2A activity towards T is regulated, an in vitro assay to study the process of T dephosphorylation was developed. Unlabeled extracts from cells enriched for various stages of the cell cycle were incubated with 32P-labeled, immunocomplexed T. Extracts from a population of cells enriched for S phase demonstrated a selective ability to dephosphorylate this labeled protein when compared with extracts prepared from G1- and M-phase cells. The time course of release from growth arrest demonstrated that this T-specific phosphatase activity occurred at the onset of host-cell DNA synthesis. In contrast, when using 32P-labeled phosphorylase a as the substrate, phosphatase activity appeared to be present throughout the cell cycle. The data presented here are consistent with the notion that PP2A activity towards T is regulated in a cell cycle-dependent manner.
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PMID:Selective ability of S-phase cell extracts to dephosphorylate SV40 large T antigen in vitro. 131 15

The biochemical mechanisms involved in neurite outgrowth in response to nerve growth factor (NGF) have yet to be completely resolved. Several recent studies have demonstrated that protein kinase activity plays a critical role in neurite outgrowth. However, little information exists about the role of protein phosphatases in the process. In the present study, okadaic acid, a phosphatase inhibitor (specific for types 2A and 1) and tumor promoter, was used to investigate the role of protein phosphatases in neurite outgrowth in PC12 cells. PC12 cells cultured in the presence of 50 ng/ml of NGF started to extend neurites after 1 day. After 3 days, 20-25% of the cells had neurites. Okadaic acid inhibited the rate of neurite outgrowth elicited by NGF with an IC50 of approximately 7 nM. This inhibition was rapidly reversed after washout of okadaic acid. Okadaic acid also enhanced the neurite degeneration of NGF-primed PC12 cells, indicating that continual phosphatase activity is required to maintain neurites. Taken together, these results reveal the presence of an okadaic acid-sensitive pathway in neurite outgrowth and imply that protein phosphatase plays a positive role in regulating the neuritogenic effects of NGE.
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PMID:Okadaic acid, a protein phosphatase inhibitor, inhibits nerve growth factor-directed neurite outgrowth in PC12 cells. 132 35

A 13-year-old boy with an anaplastic meningioma at the site of the jugular foramen had an increased serum level of aklaline phosphatase (ALPase) (liver form) in the serum before surgery. Immediately after excision of the tumor, the serum ALPase level decreased dramatically. Histochemical and immunohistochemical examinations revealed ALPase activity (liver form) in the neoplastic cells. This case would be the third with clinical evidence that the increased level of serum ALPase is of neoplastic cell origin from the meningioma. The implications of ALPase in brain tumors are discussed.
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PMID:High serum alkaline phosphatase level of meningioma cell origin: case report and review of the literature. 137 54

We describe a case of gastric cancer with multiple liver metastasis that clearly decreased in size after administration of 5'-DFUR. The patient (a 63-year-old male) was inoperable because of multiple liver metastasis. 5'-DFUR 600 mg/day reduced the size of the multiple liver tumors (reduction rate 90%, partial response for four months), but the gastric tumor was unaltered. A rapid decrease in alkali-phosphatase indicated reduction of the liver tumors only one week after the initiation of 5'-DFUR.
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PMID:[A case report; 5'-DFUR reduced gastric cancer with multiple liver metastasis]. 138 90

Experiments were performed using an established human glioblastoma cell line to determine the effect of lipoproteins on regulating their growth. It was found that synthetic and natural human high density lipoproteins (HDL) were effective in inhibiting tumor cell growth in a nontoxic, dose-dependent manner, and that the LD50 was 10-fold lower than that for normal rat astrocytes grown under identical conditions. In the presence of the antioxidant, glutathione, essentially all of the growth-inhibiting properties of HDL could be reversed suggesting that oxidized lipids from the HDL interacting with the plasma membranes of the glioblastoma cells were responsible for the growth-inhibiting effect observed. The markedly lower concentration of HDL required to inhibit glioblastoma cells in culture compared to normal astrocytes suggested that the mechanism of HDL-induced inhibition may be important for tumor growth in vivo. One possible mechanism under investigation is the possibility of HDL modulation of a membrane-associated, tumor-specific phosphatase.
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PMID:The effect of lipoproteins on human glioblastoma growth in vitro. 141 23

We have cultured cells from explants of a human cementum tumor. The cells obtained were multipolar, they formed network-like structures and they were alkaline-phosphatase positive. Immunostaining and Western blots using specific antibodies revealed that these cells produced bone sialoprotein and collagen types I and V, and they also mineralized in vitro. Conditioned medium was mitogenic to fibroblasts and mitogens present were separated by heparin-affinity chromatography. Based on affinity to heparin and antibody-inhibition studies, the heparin fractions were shown to contain cementum-derived growth factor, platelet-derived growth factor and fibroblast growth factors. The cementum tumor cells, but not gingival fibroblasts, were stained positively by an antibody to cementum-derived attachment protein. The attachment protein was separated by immunoaffinity chromatography, and Western blots revealed that the preparation contained 56-kDa and 43-kDa proteins as major bands. Cells pulse-labeled with radioactive amino acids contained a 43-kDa protein as the major component; however, this protein was absent after a cold chase in the presence of cycloheximide, but 56-kDa, 39-kDa and 26-kDa species became prominent. These data indicated that the 56-kDa cementum attachment protein is derived from a 43-kDa precursor. Our data show that the cells cultured from the cementum tumor represent cementum cells capable of synthesizing and secreting cementum proteins in culture.
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PMID:Isolation of human tumor cells that produce cementum proteins in culture. 142 95

Protein kinase C (PKC) is the major cellular receptor for tumor promoting phorbol esters. Phorbol esters activate alpha-, beta-, delta- and epsilon-PKCs in GH4C1 rat pituitary cells and cause their redistribution from a soluble to a particulate fraction. We have now characterized the effect of several non-phorbol ester tumor promoters on PKC isozyme distribution in GH4C1 cells. The incomplete tumor promoter mezerein caused redistribution of alpha-, beta-, delta- and epsilon-PKCs. Thus, it did not display partial agonist activity. The phosphatase inhibitor okadaic acid did not cause redistribution of any isozyme. The calcium ATPase inhibitor thapsigargin and the ser/thr kinase inhibitor staurosporine caused redistribution of epsilon-PKC and, to a lesser extent, delta-PKC. Although the mechanism of the selective effect on delta- and epsilon-PKCs is not yet known, these data clearly demonstrate that their subcellular distribution can be regulated by a pathway that does not influence alpha- and beta-PKCs. Phorbol ester activation of epsilon-PKC was associated with appearance of a more slowly migrating immunoreactive band in the particulate fraction. Both epsilon-PKC forms accumulated phosphate during phorbol ester treatment. The phosphorylated forms of epsilon-PKC were preferentially recovered in the particulate fraction. Although staurosporine caused redistribution, it prevented the phorbol dibutyrate (PDBu)-mediated appearance of the upper band of the doublet and the increased phosphorylation of both bands. The PDBu-mediated redistribution of alpha- and beta-PKCs was not inhibited by staurosporine, even though staurosporine effectively inhibited PKC catalytic activity. Therefore, catalytic activity is not required for redistribution.
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PMID:Selective redistribution of protein kinase C isozymes by thapsigargin and staurosporine. 142 67

A minisatellite-binding protein, Msbp-4, with a molecular mass of 35 kDa has been purified from mouse tumor cells that binds to hypervariable Pc-1 and Pc-2 minisatellites. The binding is much more efficient than that to genetically stable minisatellite homologues. As assayed by Southwestern analysis, Msbp-4 favors multiple copies of the Pc-2 repeat sequence GGCAGGA and requires the cytosine-rich single strand for the binding. The activity is also present in extracts from mouse testis but not from liver. The phosphatase treatment revealed that Msbp-4 is phosphorylated and may have a regulatory function, because dephosphorylation affects the activity and specificity of the binding. Sequence preference is demonstrated by a competition experiment using single-base substitution mutants. Thus, the binding properties of Msbp-4 observed here lead to an implication that the protein-DNA complexes result in formation of a single-stranded DNA loop of the G-rich strand in the minisatellite which may enhance the ability of the minisatellite to undergo recombination.
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PMID:A 35-kDa protein binding to a cytosine-rich strand of hypervariable minisatellite DNA. 160 95

The effect of phosphorylation on the hormone-binding capacity of the estrogen receptor (ER) was investigated in hormone-dependent (HD) and hormone-independent (HI) mammary carcinomas of GR mice. Tumor cytosols were incubated with ATP under conditions previously used to study the tyrosine kinase which confers hormone binding to phosphatase-treated or in vitro-synthesized ER. The ATP-dependent increases in hormone-binding capacity of 8 out of 20 HI tumors ranged from values of 23 to 124 fmol/mg cytosol protein. The enhancement by ATP of hormone binding to ER was significantly less marked in HD and HR tumors than in HI tumors. In only 3 out of 13 HD and HR tumors was an increase ranging from 15 to 20 fmol/mg protein detected. Analysis by Scatchard plot of estradiol binding to ER showed that cytosol incubation of HI tumors with ATP markedly increased the hormone binding without any change in affinity. The data suggest that ER of HI tumors is less phosphorylated in vivo than the ER of HD/HR tumors, so that the receptor of HI tumors is more susceptible to gamma-32P-ATP phosphorylation and ATP-induced hormone binding in vitro. Western blot of ER with antiphosphotyrosine antibody showed that, in HI tumors, the large ATP-induced increase in hormone binding to ER was associated with phosphorylation on tyrosine of the receptor itself. Our findings indicate that the process of activation-inactivation of binding through tyrosine-phosphorylation/phosphotyrosine-dephosphorylation of ER observed in estrogen target tissues is altered in some HI mammary tumors.
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PMID:Phosphorylation and estradiol binding of estrogen receptor in hormone-dependent and hormone-independent GR mouse mammary tumors. 161 82

The activity of aminoacyl-tRNA synthetase phosphatase as well as the activities of aminoacyl-tRNA synthetases in Krebs II ascites cells and MPC-11 cells have been investigated. The activity of the phosphatase was greater in the tumor cells than in normal tissues. The aminoacyl-tRNA synthetase activities were 100-300 times higher than the activities found in the uterus of ovariectomized mice, but not very different from the activities found in the liver. The influence of cyclic AMP. 2-deoxyadenosine 3-phosphate and 2-deoxyguanosine 3-phosphate on the growth of MPC-11 cells, grown in suspension culture, was also investigated.
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PMID:The activities of aminoacyl-tRNA synthetase phosphatase and aminoacyl-tRNA synthetases in MPC-11 and Krebs II ascites cells. 164 85


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