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)

Total superoxide dismutase (SOD) and manganese superoxide dismutase (Mn SOD) specific activities were measured in tissue homogenates and in isolated mitochondria from normal rat liver and three Morris hepatomas of different growth rates. Total SOD and Mn SOD specific activities were decreased in all tumor homogenates when compared to normal liver; the lowest activity was associated with the fastest growing tumor. These results are consistent with the hypothesis that total Mn SOD specific activity is decreased in all tumors. The Mn SOD specific activity was similar to the total SOD specific activity of isolated mitochondria, indicating that mitochondrial SOD is almost entirely manganese containing. This activity was decreased in the fast- and medium-growth-rate hepatomas but was slightly increased in the tumor with the slowest growth rate when compared to liver. The normal or higher than normal mitochondrial Mn SOD specific activity indicates that decreased mitochondrial SOD specific activity is not a characteristic of all tumors. Superoxide radical (O2-.) formation was measured in submitochondrial particles obtained by sonication of isolated mitochondria and subsequent washings to remove the SOD. The difficulty encountered in reducing the SOD activity suggests that at least part of the mitochondrial SOD might be associated with the mitochondrial membrane. In liver submitochondrial particles, O2-. was formed only when succinate and antimycin A were used together, as substrate and inhibitor of the electron transport chain, respectively. In the hepatomas studied for O2-. production (slow- and fast-growth rates), the formation of the radical was detected in the presence of succinate even when no inhibitor was present. Antimycin A stimulated the production of O2-. in normal rat liver and slow-growth-rate tumor, but not in fast-growth-rate tumor submitochondrial particles. Reduced nicotinamide adenine dinucleotide did not lead to the production of O2-. by normal liver or hepatoma submitochondrial particles. Mitochondrial membrane damage was seen in micrographs of the medium- and fast-growing hepatomas. This could be a consequence of low mitochondrial SOD concomitant with a flux of superoxide, if the radical is produced in vivo by these mitochondria.
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PMID:Superoxide dismutase and superoxide radical in Morris hepatomas. 625 38

Malignant cells of the mouse transformed by a variety of different agents have been found to express high levels of a 53,000 Mr phosphoprotein (designated p53). Little or no p53 can be detected in normal mouse cells. The nucleus appears to be the predominant site of p53 localization in transformed cells. p53-related antigens are also found in transformed cells of rat, hamster, rabbit, and human. In cells transformed by simian virus 40 (SV40), p53 forms a complex with SV40 tumor (t) antigen, resulting in the coprecipitation of T antigen by monoclonal p53 antibodies. Immune complexes of p53 precipitated from extracts of SV40- or methylcholanthrene-transformed cells by monoclonal p53 antibodies have protein kinase activity. This enzymatic activity is dependent upon divalent cations, utilizing Mn2+ more effectively than Mg2+. The phosphorylation of p53 in this kinase reaction has been found to involve serine and threonine, but not tyrosine residues. In view of the finding that the transforming proteins of several different oncogenic viruses have kinase activity, the association of this activity with p53 is important with regard to the possibility of a common pathway of transformation by diverse agents.
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PMID:p53 transformation-related protein: detection of an associated phosphotransferase activity. 626 26

Incubation of membranes prepared from A431 cells with either epidermal growth factor (EGF) or phorbol 12-myristate 13-acetate (PMA) stimulates the transfer of 32phosphate from [gamma-32P]ATP into 8-10 membrane proteins. The major phosphorylated protein migrates on NaDodSO4/polyacrylamide gels with an apparent Mr of 180,000, corresponding to the previously identified EGF receptor. Stimulation of EGF receptor phosphorylation by PMA does not require Ca2+, suggesting that prior activation of protein kinase C is not a prerequisite for phosphate transfer. PMA-enhanced phosphorylation proceeds at 4 degrees C and requires Mn2+, both properties of tyrosine-specific protein kinases. Phospho amino acid analysis of the Mr 180,000 receptor band shows that only tyrosine residues are phosphorylated when A431 membranes are treated with either EGF or PMA. Moreover, proteolysis reveals that these residues are located in the same peptides of the receptor. These results demonstrate that a potent tumor-promoting phorbol ester can mimic a critical early response usually elicited by EGF.
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PMID:Phorbol esters potentiate tyrosine phosphorylation of epidermal growth factor receptors in A431 membranes by a calcium-independent mechanism. 632 19

The presence of a soluble, Mg2+- or Mn2+-dependent p-nitrophenylphosphatase activity in Ehrlich ascites tumor cell homogenates is reported. The crude homogenate was fractionated over Sephadex G-150 gel-filtration and DEAE-Sephacel anion-exchange columns, and two p-nitrophenylphosphatase activities were resolved. The most active fraction, Peak I, was characterized and found to be similar to phosphotyrosyl-protein phosphatases characterized elsewhere in that it has optimal activity at neutral pH; it is inhibited by phosphate, Zn2+, and vanadate; and it is not inhibited by levamisole. However, Peak I differs from phosphotyrosyl-protein phosphatases in that Mg2+ or Mn2+ is required for activity, fluoride is an inhibitor, and pyrophosphate is not inhibitory. Inhibition by the phosphorylated compounds phosphotyrosine, phosphoserine, phosphothreonine, ATP, CTP, GTP, ITP, NADP, fructose 6-phosphate, glucose 1-phosphate, galactose 1-phosphate, 2-phosphogluconic acid, and 6-phosphogluconic acid was also observed. Ehrlich ascites tumor cell p-nitrophenylphosphatase is shown to be sensitive to inactivation by trypsin, N-ethylmaleimide, or heat treatments.
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PMID:Mg2+- or Mn2+-dependent p-nitrophenylphosphatase activity is present in Ehrlich ascites tumor cells. 633 18

Previous studies indicated that accumulation of alpha-fucosyl-GM1 (IV2FucII3NeuAcGgOse4Cer) and alpha-galactosyl-alpha-fucosyl-GM1 (IV3GalIV2FucII3NeuAcGgOse4Cer) occurs in precancerous livers of rats fed the chemical carcinogen N-2-acetylaminofluorene, before development of hepatoma. Both fucogangliosides were completely absent in normal rat liver as well as in livers of rats fed a nonhepatic carcinogen and tumor promoters (Holmes, E.H., and Hakomori, S. (1982) J. Biol. Chem. 257, 7698-7703). The enzymatic basis of the chemical changes described above is reported in this paper. The alpha-L-fucosyltransferase activity toward GM1 (II2NeuAcGgOse4Cer) as well as asialo-GM1 (GgOse4Cer) was almost undetectable in extracts from normal rat liver, but significant activity of this enzyme was detected in extracts of rat livers after 4 weeks of feeding a diet containing N-2-acetylaminofluorene. The same enzyme activity in cultured rat hepatoma cells was 18- to 47-fold higher than in N-2-acetylaminofluorene-fed rat liver. In contrast, alpha-galactosyltransferase activity with a broad substrate specificity was detected in normal as well as in N-2-acetylaminofluorene-fed liver, although the specific activity of this enzyme in Golgi membranes in precancerous liver was significantly higher than that of normal rat liver. Thus, the appearance of alpha-fucosyl-alpha-galactosyl-GMI in precancerous liver is due to an induction of synthesis of alpha-fucosyl-GMI which is the substrate for the normally existing alpha-galactosyltransferase. The activity of alpha-fucosyltransferase was highly specific toward a substrate structure Gal beta 1 leads to 3GalNAc beta 1 leads to R in GMI or asialo-GMI and showed an anomalous inhibition by a large variety of detergents tested. In contrast, the alpha-galactosyltransferase showed a wide substrate specificity, activated by detergents and Mn2+ ion. Membrane alterations in precancerous and malignant transformation of rat liver is associated with an induction of an unusual alpha-fucosyltransferase which is the key step in synthesis of both fucogangliosides.
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PMID:Enzymatic basis for changes in fucoganglioside during chemical carcinogenesis. Induction of a specific alpha-fucosyltransferase and status of an alpha-galactosyltransferase in precancerous rat liver and hepatoma. 640 18

Zn2+ potentiates binding of the 4.5S [3H]dihydrotestosterone-receptor complex to isolated rat prostate Dunning tumor nuclei in vitro when assayed in the presence of 300 microM ZnCl2, 3 mM MgCl2, 0.25 M sucrose, 5 mM mercaptoethanol, 0.15 M KCl, and 50 mM tris(hydroxymethyl)aminomethane, pH 7.5. In the presence of 5 mM mercaptoethanol, the concentration of 50 microM total Zn2+ required to promote half-maximal receptor binding to nuclei corresponds to a free Zn2+ concentration of 50 nM. The receptor-nuclear interaction appears to be selective for Zn2+; other divalent cations when added at a concentration of 1 mM to a buffer containing 5 mM mercaptoethanol are less effective (Ni2+) or have essentially no effect (Ca2+, Mg2+, Mn2+, Co2+, Cu2+, and Cd2+). Zn2+ does not alter the sedimentation rate of the 4.5S [3H]dihydrotestosterone receptor in the presence of mercaptoethanol; however, in the absence of mercaptoethanol, Zn2+ causes the receptor to aggregate. Zn2+-dependent nuclear binding of the 4.5S [3H]dihydrotestosterone receptor is saturable at 1.4 X 10(-13) mol of receptor sites/mg of DNA, corresponding to approximately 1150 sites/nucleus. In the presence of excess nuclei, up to 60% of added receptor is nuclear bound. An apparent binding constant for the receptor-nuclear interaction of 10(13) M-1 was approximated. Pyridoxal 5'-phosphate (less than or equal to 10 mM), but not 0.4 M KCl, inhibits Zn2+-dependent nuclear binding of the [3H]dihydrotestosterone receptor. Up to 66% of nuclear-bound receptor can be extracted in buffer containing 3 mM ethylenediaminetetraacetic acid plus either 0.4 M KCl or 10 mM pyridoxal 5'-phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Zinc potentiation of androgen receptor binding to nuclei in vitro. 646 48

Histologically normal and neoplastic human breast tissues obtained from 25 patients at the time of mastectomy were homogenized (200 mg/ml) in distilled water and 5-microliter aliquots dried on Formvar films for trace element analysis by energy-dispersive X-ray fluorescence. The elements measured were calcium, vanadium, copper, zinc, iron, chromium, manganese, nickel, selenium, molybdenum, bromine, rubidium, strontium, mercury, arsenic, and lead. In general, significantly large increases (p less than 0.001) in calcium, vanadium, copper, zinc, selenium, and rubidium were found in breast tumors, with a less significant increase (p less than 0.05) for nickel. When a comparison was made between histologically normal and neoplastic tissues from the same individual, zinc and rubidium were found to be consistently higher in the tumor, whereas calcium, copper, and vanadium levels varied from normal to high. In no instance were the tissue changes in calcium, copper, zinc, or rubidium reflected in the blood levels, which were within normal limits. The distribution of calcium, copper, and zinc in urine varied among individuals with primary tumors; however, rubidium levels tended to be consistently elevated. An attempt is being made to correlate these various differences with the extent of the primary disease at the time of surgery, the postoperative tumor-free interval, and subsequent therapy.
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PMID:Comparison between concentrations of trace elements in normal and neoplastic human breast tissue. 648 92

The major species of tyrosine protein kinase of rat liver, has been purified to near homogeneity from liver cytosol. When the kinase was incubated with MnCl2 and [gamma-32P]ATP, two phosphoproteins with molecular masses of 72 and 75 kilodaltons were observed. The purified kinase, called p75 kinase, phosphorylates [Val5]angiotensin II, casein, vinculin, and a 34-kilodalton protein isolated from chicken embryo fibroblasts. However, it does not phosphorylate histones or IgG from Rous sarcoma virus tumor-bearing rabbits. The kinase does not contain any of the major antigenic determinants found in retroviral tyrosine protein kinases or in epidermal growth factor-receptor kinase. p75 kinase activity, as well as viral tyrosine protein kinase activity, is stimulated by heparin. Phosphorylation of angiotensin is also stimulated by high ionic strength. In contrast, casein phosphorylation by the kinase appeared to be inhibited by high salt. Kinetic properties of p75 kinase have been determined and have revealed some striking differences from those of most other tyrosine protein kinases. For instance, p75 kinase exhibits rather stringent dependence for its activity on ATP as phosphoryl donor and Mn2+ as divalent cation.
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PMID:Purification and characterization of the major species of tyrosine protein kinase in rat liver. 653 79

Solid tumors were induced by implantation of 5 X 10(6) Ehrlich carcinoma cells im into the right flank of 8- to 12-week-old female CBA/J mice. Tumor-bearing mice were killed at 0, 2, 4, 10, or 24 days after im implantation of the tumor cells, and superoxide dismutase (SOD) activities were determined in liver, spleen, kidneys, lungs, and leg muscle. Depressed SOD activities were seen in all organs studied. In liver, spleen, and kidneys, the manganese SOD (MnSOD) activities were depressed at some point after implantation, even though microscopic examination revealed no evidence of metastases in these organs. Cytochrome c oxidase activity was not diminished in any of the tissues studied, indicating that the decline in MnSOD was not due to a decline in the number of mitochondria or to a general decline in mitochondrial enzymes. When the tumor cells were dialyzed against 0.9% saline, the dialysate contained a factor that when injected im also inhibited SOD activity.
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PMID:Lowered superoxide dismutase activity in distant organs of tumor-bearing mice. 658 84

A polypeptide-dependent protein kinase was purified about 80-fold from an extract of plasma membranes of Ehrlich ascites tumor cells. The membranes were extracted with Nonidet P-40, and the extract was purified by ammonium sulfate fractionation and hydroxylapatite and affinity chromatography. The activity was stimulated 10-fold or more by polypeptide preparations from a variety of tissues, including placenta and hypothalamus. Polypeptide-dependent protein kinase had a pH optimum of about 7.5 and required Mg2+ for activity. Mn2+ at low concentrations (200 microM) stimulated enzyme activity somewhat but inhibited activity strongly at higher concentrations. The best available substrate for polypeptide-dependent protein kinase was beta-casein, and little or no phosphorylation was observed with alpha-casein, kappa-casein, phosvitin, alpha-lactalbumin, alpha-lactoglobulin, and histone. However, several endogenous substrates from plasma membranes of Ehrlich ascites tumor cells were phosphorylated. Polypeptide-dependent protein kinase activity was not inhibited by 10 mM N-ethylmaleimide, and this resistance was useful in differentiating this protein kinase from other protein kinases that were present in crude fractions and sensitive to the inhibitor.
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PMID:New protein kinase from plasma membrane of Ehrlich ascites tumor cells activated by natural polypeptides. 658 91


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