Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ornithine decarboxylase (ODC) is present in all nucleated cells and is the rate-limiting enzyme for synthesis of polyamines. In turn, the polyamines are required for DNA synthesis and cell growth. In Reuber H35 hepatoma cells, we show that ODC activity is increased by about 50% during exposure to a 1-h "athermal" (less than 0.1 degree C temperature rise) (450 MHz, 1.0 mW/cm2 peak-envelope-power) microwave field sinusoidally amplitude-modulated at 16 Hz. The increased activity of ODC persisted for several hours following the 1-h exposure to the field. A similar field amplitude-modulated at 60 and 100 Hz did not alter the hepatoma cell ODC activity. The stimulated ODC activity in the cultured cells that followed treatment with a phorbol ester tumor promoter (12-O-tetradecanoylphorbol-13-acetate) was further potentiated by prior exposure to the same low energy electromagnetic field. This field did not alter either basal or 12-O-tetradecanoylphorbol-13-acetate-stimulated DNA synthesis. We observed a similar increase in the basal ODC activity of cultures of two additional cell lines (Chinese hamster ovary; and 294T melanoma) exposed for 1 h to the amplitude-modulated field. Chinese hamster ovary cells exposed to the radio frequency field for 1 h also responded to subsequent treatment with 12-O-tetradecanoylphorbol-13-acetate by exhibiting a further increase in ODC activity. We have observed previously that the activity of this enzyme is increased in cultured cells following a transient exposure to a 60-Hz electric field. Altered ODC activity may serve as a sensitive and specific molecular marker of the transductive coupling of weak pericellular electromagnetic fields to biological systems.
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PMID:Increased ornithine decarboxylase activity in cultured cells exposed to low energy modulated microwave fields and phorbol ester tumor promoters. 339 Aug 16

The enzyme ornithine decarboxylase (ODC; EC 4.1.1.17) catalyses the first and rate-limiting step in polyamine biosynthesis. Its activity is markedly increased in rapidly growing or regenerating tissue and is subject to regulation by a variety of trophic and mitogenic stimuli. ODC is therefore believed to play an essential role in the onset of cellular proliferation. In a molecular-biological approach to investigate ODC regulation upon induction by tumor promoters in rat liver we isolated an almost full-length rat ODC cDNA clone of 2.4 kb (designated pODC.E10) from a cDNA library of testosterone-induced rat kidney poly(A)+ RNA. Characterization by restriction-endonuclease mapping and sequence analysis showed strong homology to mouse ODC cDNA sequences previously published [Gupta and Coffino, J. Biol. Chem. 260 (1985) 2941-2944; Kahana and Nathans, Proc. Natl. Acad. Sci. USA 82 (1985) 1673-1677; Hickok et al., Proc. Natl. Acad. Sci. USA 83 (1986) 594-598]. This homology is most pronounced in the 461-aa-spanning coding region, amounting to 94% and 97% at the DNA and protein levels, respectively. In the 423-nt 5' leader the rat-mouse homology (approx. 75%) is most pronounced in a region of about 175 nt directly upstream from the translational start site. The leader sequence also contains a perfect inverted repeat of 54 nt and ten additional upstream ATG triplets, which are all followed by nonsense codons before the initiating ATG. In the 633-nt 3' trailer region of pODC.E10 an additional polyadenylation signal is observed more than 300 nt upstream from the 3' end. Rat-mouse homology is about 80% up to this first polyadenylation signal and is considerably less thereafter. The presence of two alternate polyadenylation sites most likely accounts for the 3' size heterogeneity observed in the two ODC mRNAs of 2.1 and 2.6 kb, respectively. In rat liver both mRNAs are coordinately induced by different tumor promoters. Finally, Southern blot analysis of normal rat liver and rat hepatoma DNA revealed that rat ODC, as in other rodents, belongs to a multigene family.
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PMID:Cloning and nucleotide sequence of rat ornithine decarboxylase cDNA. 344 98

A number of amino acids, most noticeably asparagine, were capable of inducing ornithine decarboxylase in H-35 rat hepatoma cells. The effective amino acids were all neutral and were substrates of the Na+-dependent transport systems A, ASC and N. Transport inhibitor studies indicated that there was an excellent correlation between the level of enzyme activity induced and the initial rate of asparagine transport into the cells by the A and the N systems. It is proposed that the activation of the Na+-dependent, pH-sensitive amino acid transport systems and the subsequent intracellular pH and ionic perturbation constitute part of the initiation signals for cell activation.
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PMID:Asparagine transport and the induction of ornithine decarboxylase in H-35 rat hepatoma cells. 345 89

The hepatic levels of 5'-deoxy-5'-methylthioadenosine (MTA) were measured in the livers of adult male Sprague-Dawley rats a) killed at various times during the liver regeneration process, b) killed at times after partial hepatectomy when the liver mass had already been completely restored (hereafter called post-regeneration livers), or c) continuously fed 3'-methyl-4-dimethyl-aminoazobenzene (CAS: 55-80-1) up to the full development of hepatoma and killed at regular intervals during hepatocarcinogenesis. Hepatic MTA levels were always significantly decreased, although to different degrees in both in vivo models of hepatic growth and at all times during the investigation. Astonishingly, the MTA levels were also significantly decreased in the post-regeneration livers, in which there was also a significant increase in the activity of adenosylmethionine decarboxylase (S-adenosyl-L-methionine decarboxylase; EC 4.1.1.50) with normal levels of activity of ornithine decarboxylase (EC 4.1.1.17). These results demonstrate that a) the MTA content is always decreased in rat liver whenever this organ is involved in a proliferative process (whether controlled or uncontrolled); b) the decrease in hepatic MTA content is a biochemical feature necessary for, but by no means by itself sufficient for, hepatocyte proliferation to occur, since this decrease remains long after complete restoration of the liver mass; and c) the return of the hepatocytes to the normal biochemical program after restoration of the liver mass is not complete, even though these cells become quiescent, because there are still some biochemical abnormalities in the post-regeneration livers.
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PMID:Persistently decreased hepatic levels of 5'-deoxy-5'-methylthioadenosine during regeneration of and chemical carcinogenesis in rat liver. 345 57

Present results concern a microsome-bound enzymatic system which has been recognized as responsible for the rapid inactivation in vitro of ornithine decarboxylase (ODC). Two different models have been investigated: a) rat liver after a single thioacetamide administration, and b) the 3924 A Morris hepatoma. In both these models we observed variations in the microsome-bound ODC-inactivating capacity. In parallel, changes in ODC properties were observed. The possibility of a causal relationship between the two events is discussed. The actual role of the microsome-bound ODC-inactivating system, in ODC activity regulation in vivo cannot be established, but it remains as a fairly plausible working hypothesis.
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PMID:Different factors possibly involved in post-translational regulation of ornithine decarboxylase activity. 354 68

A strong ornithine decarboxylase (ODC)-inactivating capacity has been previously shown (M.F. Zuretti and E. Gravela (1983) Biochim. Biophys. Acta, 742, 269-277) to be bound to rat liver microsomes. Present results show that in 2 fast-growing transplantable tumors, the 3924A Morris hepatoma and the AH 130 Yoshida ascites hepatoma, microsomes are endowed with a greatly enhanced ODC-inactivating capacity, and, concurrently, ODC displays an extreme in vitro liability and an unusual thiol-dependency (most of the activity requires dithiothreitol supply to be determined). These data are at variance with those previously obtained in hepatomas induced by N-2-fluorenylacetamide (E. Gravela et al., (1983) Cancer Res., 42, 2298-2300). The possibility that ODC liability in the 2 hepatomas here studied may result from in vivo exposure to a strong microsomal activity is considered.
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PMID:Ornithine decarboxylase lability in 2 transplantable highly deviated rat hepatomas. 358 Oct 55

We have studied the activity, thiol-dependency and Km of ornithine decarboxylase (ODC) from the following sources: liver of rats subjected to partial hepatectomy or administered thioacetamide, the rat 3924A Morris hepatoma, the rat AH130 Yoshida ascites hepatoma, a mouse transplantable mammary carcinoma and kidney of rats administered testosterone propionate. In order to detect possible changes occurring during in vivo ageing of this enzyme we inhibited protein synthesis with cycloheximide. A gradual decrease of Km during ageing was observed in ODC from liver.
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PMID:Studies on ornithine decarboxylase from liver, kidney and tumoral tissues during activity decay following cycloheximide administration. 362 58

The contribution of changes in mRNA levels to the induction of ornithine decarboxylase (ODC) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in rat H35 hepatoma cells was analyzed by Northern blot and quantitative dot blot hybridization. ODC mRNA accumulated rapidly in TPA-treated cultures. The increase in message was transient, reaching a peak within about 3 h, then declining to control levels after 18 h. Maximal accumulation of ODC-specific mRNA varied from 3- to 8-fold above control. The TPA dose-response for ODC message accumulation was half-maximal at approximately 0.18 microM TPA. The increase was completely blocked by actinomycin D, suggesting that TPA stimulates the transcription of ODC genes. Inhibition of protein synthesis by cycloheximide (10 micrograms/ml) led to a superinduction of ODC mRNA in the presence of TPA, which suggested that a short-lived protein may be responsible for negative control of ODC expression.
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PMID:Transient induction of ornithine decarboxylase mRNA in rat hepatoma cells treated with 12-O-tetradecanoylphorbol-13-acetate. 363 1

People living in the industrial society of today are unavoidably exposed to low-energy electromagnetic (EM) radiation. The potential risk to human health of such exposure has received much study. In this regard, numerous epidemiological studies have linked exposure to low-energy EM fields to increased cancer risk. We investigated the ability of low-energy 60-Hz EM fields to alter the activity of ornithine decarboxylase (ODC) in a number of established cell lines. The activity of ODC, the controlling enzyme in polyamine biosynthesis, has been shown to be elevated in growing cells or tissues and during the process of tumor promotion. A 1-h exposure to a 60-Hz EM field of an intensity of 10 mV/cm produced a 5-fold increase in ODC activity in human lymphoma CEM cells and a 2- to 3-fold increase in mouse myeloma cells (P3) relative to the unexposed cultures. Depending upon the cell type, ODC activity increased during the 1-h exposure period and remained elevated for several hours after the field exposure ended. In another series of experiments, fields of an intensity as low as 0.1 mV/cm for a 1-h period produced a 30% increase in the activity of ODC in Reuber H35 hepatoma cells grown in monolayer culture. In the H35 cells, continuous exposure to the 60-Hz EM field (10 mV/cm) for periods of 2 and 3 h resulted in either no increase in ODC activity (2 h) or a decrease in enzyme activity (3 h) compared to the unexposed control cultures. The data is discussed in relation to possible molecular mechanisms of field-cell interaction, the importance of the exposure intervals altering cellular ODC activity and the potential ability of 60-Hz EM fields to serve as a tumor promoting stimulus.
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PMID:The effects of low-energy 60-Hz environmental electromagnetic fields upon the growth-related enzyme ornithine decarboxylase. 365 76

The polypeptide growth factors, nerve growth factor, epidermal growth factor, and platelet-derived growth factor, as well as insulin do not induce ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) unless a minimal concentration of an ornithine decarboxylase-inducing amino acid, such as asparagine, is present in the medium. The effects of the growth factors were studied in appropriately responsive cell lines: pheochromocytoma (PC12) cells for nerve and epidermal growth factors, fibroblasts (NIH 3T3) for platelet-derived growth factor, and fibroblasts and hepatoma (KRC-7) cells for insulin. The nonmetabolizable amino acid analog alpha-aminoisobutyric acid can replace asparagine, indicating that the covalent modification of the inducing amino acid is not necessary for the induction of ornithine decarboxylase by these growth factors. For the same intracellular concentration of the inducing amino acid, the presence of the growth factors induces higher levels of ornithine decarboxylase. The evidence indicates that these growth factors do not induce ornithine decarboxylase by raising the intracellular concentration of amino acids but rather act synergistically with the inducing amino acid. Evidence is provided that the induction of polyamine-dependent growth by these growth factors is mediated by amino acids. The relationship of these results to the A and N amino acid transport systems and to the Na+ influxes in relation to growth is discussed.
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PMID:Induction of ornithine decarboxylase activity by insulin and growth factors is mediated by amino acids. 389 32


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