Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure of isolated SENCAR mouse epidermal cells to the tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA) in vitro resulted in the production of oxidant species detected as chemiluminescence. This oxidant response can be inhibited by superoxide dismutase and copper complexes but not catalase or scavengers of hydroxyl radical or singlet oxygen, suggesting that the oxidant is superoxide anion. Inhibitors of various parts of the arachidonate cascade affect the TPA-induced oxidant response in a manner that corresponds to their effects on in vivo tumor promotion experiments. Agents that inhibit lipoxygenase activity, i.e. nordihydroguaiaretic acid, benoxaprofen, but not agents that are cyclooxygenase inhibitors, i.e. indomethacin, are effective in suppressing the oxidant response to TPA. Phospholipase C but not phospholipase A2 or D produced an oxidant response kinetically similar to that elicited by TPA. The inhibitors of TPA-induced oxidants inhibited the phospholipase C response to the same extent, suggesting that TPA and phospholipase C may produce an oxidant species through a common mechanism, via phospholipid turnover-protein kinase C activation. The relevance of oxidant production to the tumor promotion process is suggested by the ability of exogenous xanthine/xanthine oxidase, a superoxide anion-generating system, to induce ornithine decarboxylase, a characteristic of TPA-treated cells. In addition, oxidant production is significantly lower in cells from the TPA-promotion resistant C57BL/6J mouse. These studies provide further support for a role for reactive oxygens in the tumor promotion process.
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PMID:Reactive oxygen in the tumor promotion stage of skin carcinogenesis. 284 22

The role of protein kinase C in ornithine decarboxylase (ODC; EC 4.1.1.17) gene expression in primary culture of newborn mouse epidermal cells (MEC) from BALB/c mice and in skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in female CD-1 mice was determined. A time course and the dose-response curves of ODC induction paralleled that of ODC mRNA induction by TPA in MEC. TPA treatment did not elicit any change in the size of ODC mRNA. The magnitude of ODC induction was proportional to the amount of ODC mRNA increased by TPA. TPA (2 X 10(-7) M) failed to induce ODC activity in MEC plated in Ca2+-deprived medium; TPA induction of ODC could be resumed upon Ca2+ restoration in the medium. 1-Oleoyl-2-acetylglycerol, a membrane-permeable diacylglycerol which activates protein kinase C, induced at the same rate both ODC activity and the amount of ODC mRNA in MEC. Phospholipase C, which releases diacylglycerol from membrane phospholipids, also induced ODC activity; 0.02 units of phospholipase C per ml led to about a 50-fold increase in ODC activity at 6 h after treatment. Phospholipase A2 was ineffective. Phospholipase C-induced ODC activity correlated with an increased level of ODC mRNA. Furthermore, palmitoylcarnitine, an inhibitor of protein kinase C, inhibited epidermal ODC induction and the increased level of ODC mRNA by TPA. Also, palmitoylcarnitine inhibited skin tumor promotion by TPA; application of 3 mumol of palmitoylcarnitine in conjunction with each promotional treatment with 10 nmol of TPA to the initiated skin of female CD-1 mice inhibited tumor formation. Taken together, we conclude that activation of protein kinase C may be an early event in ODC gene transcription and skin tumor promotion by TPA.
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PMID:Involvement of protein kinase C activation in ornithine decarboxylase gene expression in primary culture of newborn mouse epidermal cells and in skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. 377 35

Phospholipase C (PLC), which hydrolyzes phosphoinositides, has been implicated as a key enzyme in signal transduction. We examined the expression of an isozyme of PLC, PLC-delta, in rat colon neoplasms induced by methylazoxymethanol (MAM) acetate. Large-bowel neoplasms were observed in five of 10 rats given MAM acetate (25 mg/kg body weight, by interperitoneal injection at 6 and 7 wk of age) 40 wk after treatment. Expression of PLC-delta in the neoplasms was not detected by northern blot analysis, and a low level of expression was detected by immunoblot analysis, although PLC-delta expression was apparent in the non-neoplastic colon mucosae of MAM acetate-treated rats as well as in the colon mucosae of control rats. Furthermore, analysis by reverse transcriptase-polymerase chain reaction revealed that the ratio of the expression of PLC-delta to that of beta-actin in the neoplasms was significantly lower than the ratios in the non-neoplastic colon mucosae of carcinogen-treated and control rats (P < 0.01). However, the ornithine decarboxylase (ODC) activity in the neoplasms was significantly greater than that of the non-neoplastic and control mucosae (P < 0.001). The differences in the levels of PLC-delta expression in neoplastic and non-neoplastic tissues and the inverse correlation of PLC-delta expression with ODC activity may suggest that PLC-delta has little effect on the PLC-mediated mitogenic signaling system, at least in MAM acetate-induced colon neoplasms in rats.
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PMID:Reduced expression of phospholipase C-delta, a signal-transducing enzyme, in rat colon neoplasms induced by methylazoxymethanol acetate. 752 22