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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of phorbol diesters on histone phosphorylation in BALB/c mouse lymphocytes, cells which do not respond to these agents with cell division, but with other biochemical and biological changes, was investigated. A technique for fractionating the proteins was used which was more powerful than those used previously in similar studies of phorbol diester effects on the metabolism of these proteins. Exposure of lymphocytes to tumor-promoting phorbol esters resulted in a rapid and specific increase in phosphorylation of the nuclear histone proteins H2B and H4. Within 2 hr, the phosphorylation of these two proteins rose to levels 6- to 8- and 2- to 4-fold greater, respectively, than those in control cells, when lymphocytes were exposed to 800 nM 12-O-tetradecanoylphorbol-13-acetate. Lower levels were observed with other phorbol analogues commensurate with their relative tumor-promoting abilities. Lymphocyte mitogens did not increase phosphorylation under the conditions used. The potential ability of the cell system used for defining early in vivo and in vitro phorbol diester effects, and those which are independent of cell division, is discussed.
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PMID:Specific stimulation by phorbol esters of the phosphorylation of histones H2B and H4 in murine lymphocytes. 396 42

Butylated hydroxytoluene (BHT) causes transient lung damage in mice, and it can either inhibit or enhance carcinogen induction of tumors in internal organs, such as urethan-induced lung adenomas. Since protein kinase C (Pk-C) may mediate the action of one class of tumor-modulatory agents, the phorbol esters which promote skin tumorigenesis, we are examining the hypothesis that Pk-C is involved in the modulatory effects of BHT on internal organs. Endogenous phosphorylation of a Mr 36,000 cytosolic protein (p36) with a pI of 5.7 was demonstrable in extracts from lung and spleen but not from brain or heart. Phosphorylation required the presence of both Ca2+ and phosphatidylserine, and phosphate was incorporated into seryl and threonyl residues but not into tyrosyl residues. This reaction thus has the characteristics of Pk-C-dependent catalysis. A single i.p. injection of BHT (400 mg/kg body weight) decreased p36 phosphorylation severalfold in both BALB/cByJ and A/J mice. This decrease correlated with the extent of BHT-induced lung damage with regard to both the time course following BHT administration and the dose dependence of BHT. All of the pulmonary effects of BHT are abolished if the mice are pretreated with cedrene, an inducer of drug-detoxifying enzymes. Such treatment with cedrene prevented any BHT-induced decrease in p36 phosphorylation. A decrease in Pk-C specific activity, as measured using histone as an exogenous substrate, which resulted upon BHT treatment may provide a mechanism for decreased p36 phosphorylation. The specificity of this toxicity-related effect of BHT is emphasized by the fact that urethan injection did not detectably affect the phosphorylation of any lung proteins. Both p36 phosphorylation and Pk-C specific activity increased as a function of postnatal age. Thus the extent of p36 phosphorylation was inversely related to the extent of lung cell proliferation in two different physiological states, postnatal growth and regenerative repair following BHT-induced toxic injury. A single BHT injection is sufficient to cause lung toxicity, tumor prophylaxis, or cocarcinogenesis, while tumor promotion requires chronic treatment. P36 phosphorylation also decreased when mice were given multiple BHT injections over a period of 5 weeks. These results are consistent with a hypothesis that decreased Pk-C-dependent phosphorylation of p36 is involved in lung tumor modulation by BHT.
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PMID:Decrease in the protein kinase C-catalyzed phosphorylation of an endogenous lung protein (Mr 36,000) following treatment of mice with the tumor-modulatory agent butylated hydroxytoluene. 405 47

A critical analysis of histone expression was performed on the four interspecific and the two intraspecific reconstituted cells formed between karyoplast from mouse B16 cells and the cytoplast from rat cells (L6TG.CAPr) or mouse cells (B82.CAPr). All the reconstituted cells had the same pattern of mouse histones and the same amount of mouse-specific H2B. 2 histone as that of mouse nuclear donor cells. A hybrid between B16 and L6TG.CAPr contained both mouse and rat-specific H1b subtypes, whereas no rat-specific H1b was detected in the interspecific reconstituted cells. In both intra- and interspecific reconstituted cells, the proportion of H1b content was lower than that of B16 cells but that of H1 degree was higher, indicating that the mouse H1 patterns from these cells slightly resembled the pattern of slower growing and differentiated cytoplast donor cells. As an effect of the tumor promoter, the H1 pattern tended to revert to that of the nuclear donor cells in agreement with the phenotypic reversion, without any significant change in cell growth.
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PMID:Histone expressions in mouse-rat somatic reconstituted cells. 405 27

This report demonstrates that the potent tumor promoter 12-O-tetradecanoylphorbol 13-acetate rapidly stimulates the phosphorylation of histones H2B and H4 in a cell cycle-independent manner. This effect was observed in primary cultures of BALB/c mouse splenocytes, a population of noncycling, G0 cells which are not stimulated to divide by 12-O-tetradecanoylphorbol 13-acetate treatment alone. The biological nature of this cell system allowed the analysis of histone phosphorylation in the absence of a background of cell cycle-dependent changes and in response to a nonmitogenic agent. The phosphorylation of H2B was determined with high resolution through the use of two-dimensional gel electrophoresis. In contrast to 12-O-tetradecanoylphorbol 13-acetate, the mitogen from pokeweed did not induce stimulation of H2B and H4 phosphorylation, but did, however, elicit increases in the phosphorylation of histones H1, H2A, and H3, in parallel with changes in rate of DNA synthesis.
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PMID:Specific stimulation of histone H2B and H4 phosphorylation in mouse lymphocytes by 12-O-tetradecanoylphorbol 13-acetate. 405 26

The rate of homoribopolymer-directed DNA synthesis by detergent-disrupted Moloney murine leukemia virus can be stimulated or inhibited by histone, depending on the ratio of histone to template. Of the fractions which can be separated from the whole histone, f1 causes both the greatest stimulation and the greatest inhibition. The effect of histone f1 is qualitatively similar whether the template is polyadenylate (poly A), polycytidylate, or polyuridylate, but the stimulation is greatest with poly A. The pattern of stimulation and inhibition differs, however, for a different polymerase; the DNA polymerase of Micrococcus luteus is inhibited by histone concentrations which stimulate the viral enzyme and stimulated by concentrations which inhibit the viral enzyme. For the viral enzyme, the optimum histone concentration is unaffected by changes in the virus or primer concentration; but it varies in proportion to the template concentration, suggesting that histone acts by combining stoichiometrically with the template. These data raise the possibility that a histone-like protein may participate in the synthesis of the provirus of RNA tumor viruses.
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PMID:Histones stimulate polyribonucleotide-directed polydeoxyribonucleotide synthesis by murine leukemia virus. 485 39

Data demonstrating the direct phosphorylation of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] purified from rat pheochromocytoma by ATP, Mg2+ and cyclic AMP-dependent protein kinase catalytic subunit are presented. The incorporation of phosphate is highly correlated with the activation of the hydroxylase when either the time of preincubation or the amount of protein kinase subunit is varied. The rate of phosphorylation of tyrosine hydroylase compares favorably with that of H1 histone, a known substrate of protein kinase. Lineweaver-Burk analysis of crude or purified rat pheochromocytoma tyrosine hydroxylase activity, as a function of pterin cofactor concentration, in the absence of ATP, Mg2+, and protein kinase catalytic subunit, yields a curvilinear relationship which can be resolved into two lines, suggesting two enzyme forms with different affinities for pterin cofactor. A fraction of the hydroxylase present in the tumor exists in the activated state, presumably due to the presence of ATP and endogenous protein kinase activity. When the solubl enzyme is activated by cyclic AMP, ATP, Mg2+, and protein kinase, virtually all of the enzyme is converted to the low Km state. We conclude that tyrosine hydroxylase is a substrate of cyclic AMP-dependent protein kinase in vitro and, presumably, in vivo.
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PMID:Tyrosine hydroxylase: a substrate of cyclic AMP-dependent protein kinase. 610 82

14C-arginine rich basic protein isolated from the cytoplasm of Ehrlich ascites tumor cells neutralizes the anticoagulant of activity heparin. The action of this protein is greater than H3 histone rich in arginine derived from calf thymus.
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PMID:Neutralization of heparin by basic proteins of tumor cells: studies in vitro with protein rich in 14C-arginine. 616 4

A Japanese quail embryo cell line transformed by avian retrovirus, designated QERC-31F, was further characterized in virological and cytological aspects. Infectious virus produced by this cell line was found to belong to subgroup A. The virus failed to transform quail embryo cells, whereas it induced erythroblastosis by injection into neonatal quails. Injection of QERC-31F cells into neonatal quails resulted in the induction of solid tumors which morphologically diagnosed as undifferentiated sarcoma. Mitosis of pro-erythrocytic cells with also detected in the peripheral blood of the tumor bearing animals. Antiserum to chicken erythrocyte histone V fraction which was also shown to react specifically with the nucleus of quail erythrocytes stained the nucleus of QERC-31F cells. These results suggested that this cell line maintains characteristics of the erythroblast and possibly produces avian erythroblastosis virus as well as helper virus of subgroup A.
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PMID:Japanese quail embryo cell line persistently infected with erythroblastosis virus. 618 Dec 72

The plasma membrane from the human tumor astrocytoma contains an active acid phosphatase activity based on hydrolysis of p-nitrophenyl phosphate. Other acid phosphatase substrates--beta-glycerophosphate, O-phosphorylcholine, and 5'-AMP--are not hydrolyzed significantly. The phosphatase activity is tartrate insensitive and is stimulated by Triton X-100 and EDTA. Of the three known phosphoamino acids, only free O-phosphotyrosine is hydrolyzed by the membrane phosphatase activity. Other acid phosphatases tested from potato, wheat germ, milk, and bovine prostate did not show this degree of specificity. The plasma membrane activity also dephosphorylated phosphotyrosine histone at a much greater rate than did the other acid phosphatases. pH profiles for free O-phosphotyrosine and phosphotyrosine histone showed a shift toward physiological pH, indicating possible physiological significance. Phosphotyrosine histone dephosphorylation activity was nearly 10 times greater than that seen for phosphoserine histone dephosphorylation, and Km values were much lower for phosphotyrosine histone dephosphorylation (0.5 microM vs. 10 microM). Fluoride and zinc significantly inhibited phosphoserine histone dephosphorylation. Vanadate, on the other hand, was a potent inhibitor of phosphotyrosine histone dephosphorylation (50% inhibition at 0.5 microM) but not of phosphoserine histone. ATP stimulated phosphotyrosine histone dephosphorylation (160-250%) but inhibited phosphoserine histone dephosphorylation (95%). These results suggest the existence of a highly specific phosphotyrosine protein phosphatase activity associated with the plasma membrane of human astrocytoma.
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PMID:An acid phosphatase in the plasma membranes of human astrocytoma showing marked specificity toward phosphotyrosine protein. 618 63

Histone deacetylases of Ehrlich ascites tumor cells are active at low temperatures (0-4 degrees C). The so-called hyperacetylated state of histones is the physiological state of histones in intact Ehrlich ascites tumor cells which is conserved by the continuous presence of 10 mM sodium butyrate during the preparation of nuclei and histones. Isolation of histones in the absence of butyrate causes an artificial decrease in histone acetylation. This artificial loss of histone acetylation produces a decrease of the elongation reaction in the RNA synthesis. The initiation of RNA synthesis is not affected.
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PMID:Conservation of the acetylation pattern of histones and the transcriptional activity in Ehrlich ascites tumor cells by sodium butyrate. 618 52


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