Disease relevance of ODC1

• The conserved linkage group consisting of the RRM2, ODC1, P5, and N-myc in the hamster and human genomes prompted our investigation of human neuroblastomas [1].
• Conversely, ODC activity was 3.6-fold elevated in adenocarcinomas and 3.9-fold elevated in neuroendocrine tumors compared with control pancreas [2].
• Loss of methylthioadenosine phosphorylase and elevated ornithine decarboxylase is common in pancreatic cancer [2].
• The current study evaluates the therapeutic effects of antisense ODC and AdoMetDC sequences on colorectal cancer in vitro and in vivo [3].
• Polyamine depletion by ODC-AdoMetDC antisense adenovirus impairs human colorectal cancer growth and invasion in vitro and in vivo [3].
• The United Kingdom Colorectal Adenoma Prevention participants with homozygous ODC 316AA genotype were at reduced CRA recurrence risk [relative risk (RR), 0.43; 95% confidence interval (95% CI), 0.16-1.15], particularly if also exposed to aspirin (RR, 0.24; 95% CI, 0.03-1.71) [4].

Psychiatry related information on ODC1

• Altered subcellular localization of ornithine decarboxylase in Alzheimer's disease brain [5].

High impact information on ODC1

• Mucosa from dysplastic polyps showed higher mean ornithine decarboxylase activity than mucosa from polyps that were not dysplastic (P less than 0.05) [6].
• We investigated whether the activity of ornithine decarboxylase might serve as a diagnostic test for detecting the presence of the genotype for familial polyposis [6].
• Induction of ornithine decarboxylase by nerve growth factor dissociated from effects on survival and neurite outgrowth [7].
• The ornithine decarboxylase inhibitor DL-alpha-difluoromethyl ornithine inhibited a proliferation-associated increase in ornithine decarboxylase activity in cultured human promyelocytic leukemia cells, resulting in a marked suppression of cell proliferation and subsequent cell loss [8].
• It also inhibited increases in ornithine decarboxylase activity associated with the phorbol ester-induced conversion of promyelocytic HL-60 cells to monocyte-like cells and the retinoic acid-induced conversion to granulocyte-like cells [8].

Chemical compound and disease context of ODC1

• Amplification of N-myc and ornithine decarboxylase genes in human neuroblastoma and hydroxyurea-resistant hamster cell lines [1].
• Development of resistance to hydroxyurea during treatment of human myelogenous leukemia K562 cells with alpha-difluoromethylornithine as a result of coamplification of genes for ornithine decarboxylase and ribonucleotide reductase R2 subunit [9].
• Among these tumors, the esophageal cancers had the highest ODC activity (120 +/- 43.9 pmol of CO2/h/mg of protein), compared with the stomach (37.6 +/- 13.7), colon (22.8 +/- 5.9), and liver (10.2 +/- 5.6) cancers [10].
• Differential activation of ornithine decarboxylase and tyrosine kinase in the rectal mucosa of patients with hyperplastic and adenomatous polyps [11].
• By contrast, there were no statistically significant differences in ornithine decarboxylase or polyamines between treatment groups or in those on sulindac who were polyp free compared with those who developed polyps [12].

Biological context of ODC1

• Mathematical/Statistical modeling of the data from time-course and concentration-effect experiments of gene expression from nine polyamine pathway genes represented on the HGU95Av2 chip, indicates that three biosynthetic pathway genes (SAMDC, ODC1 and SRM) are down-regulated and one catabolic pathway gene (SSAT) is up-regulated [13].
• We report here that genomic DNA from 1 of 6 primary neuroblastoma tumors containing amplified N-myc also contains amplified sequences homologous to a hamster ODC cDNA [1].
• We also show that inhibition of ODC by difluoromethylornithine caused decreased cell growth and increased apoptosis in two MTAP-deleted pancreatic adenocarcinoma-derived cell lines [2].
• Inhibition of ODC activity caused decreased cell growth and increased apoptosis in pancreatic tumor-derived cell lines [2].
• APP knockdown by RNAi verified that upregulation of ODC was APP-mediated [14].

Anatomical context of ODC1

• The genes for the M2 subunit of ribonucleotide reductase (RRM2), ornithine decarboxylase (ODC1), and 55,000-Daltons protein (P5), are amplified in hydroxyurea-resistant hamster and human cell lines [1].
• Adenovirus-mediated Expression of Both Antisense Ornithine Decarboxylase and S-adenosylmethionine Decarboxylase Induces G(1) Arrest in HT-29 Cells [15].
• Using a mouse cDNA probe for ornithine decarboxylase (ODC), we have identified and isolated an ODC cDNA clone from a lambda gt11 recombinant library prepared from human liver cell mRNA [16].
• The human ODC DNA fragments segregate with chromosome regions 2pter----p23 and 7cen----qter in mouse X human somatic cell hybrid clones containing normal, translocated, and deleted human chromosomes [16].
• Aging of IMR-90 human diploid fibroblasts in culture is accompanied by specific changes of polyamine metabolism including: (a) a fivefold decrease of serum-induced activity of ornithine decarboxylase (ODC1 EC 4.1.1.17); (b) a six to tenfold increase of polyamine catabolism; and (c) a reduction of putrescine uptake [17].

Associations of ODC1 with chemical compounds

• In addition, we examined the effect of the ODC inhibitor difluoromethylornithine on two pancreatic adenocarcinoma-derived cell lines [2].
• alpha-Difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase (ODC), was used to select two very highly drug-resistant cell lines, designated K562-DFMOr and V79-DFMOr [9].
• Apple procyanidins diminish the activities of ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase, key enzymes of polyamine biosynthesis, and they induce spermidine/spermine N(1)-acetyltransferase, which initiates retroconversion of poly-amines [18].
• Mouse Ornithine Decarboxylase-like Gene Encodes an Antizyme Inhibitor Devoid of Ornithine and Arginine Decarboxylating Activity [19].
• Herein we provide evidence for the chemical mechanism by which nitric oxide and S-nitrosothiols react with cysteine residues in ornithine decarboxylase to form an S-nitrosothiol(s) on the protein [20].

Physical interactions of ODC1

• In the present study, we show by yeast two- and three-hybrid protein-protein interaction studies that AZI interacts with all members of the antizyme family and is capable of disrupting the interaction between each antizyme and ODC [21].
• UVB radiation induces phosphorylation of the epidermal growth factor receptor, decreases EGF binding and blocks EGF induction of ornithine decarboxylase gene expression in SV40-transformed human keratinocytes [22].

Regulatory relationships of ODC1

• Antibody-bound amyloid precursor protein upregulates ornithine decarboxylase expression [14].
• Our results directly demonstrate that downregulation of AZI regulates ODC activity, intracellular polyamine levels, and cell growth through regulating antizyme activity [23].
• Finally, we describe the development and validation of a functional MYCN reporter gene assay using neuroblastoma cells (NGP) which have been stably transfected with a luciferase gene construct under control of the ornithine decarboxylase gene promoter [24].
• In the present work we have cloned the expressed human ODC gene from a genomic library of myeloma cells that overproduce ODC protein due to selective gene amplification and determined its entire nucleotide sequence [25].
• Prolactin stimulates ornithine decarboxylase and activates protein kinase C, which are pivotal enzymes in the differentiation, proliferation, and function of lymphocytes [26].

Other interactions of ODC1

• Accumulation of PNT1A cells in the S phase progressively increased at 15, 18 and 24 h of transfection with antisense ODC and/or OAZ cDNA [27].
• ODC-p has a unique mutation in cysteine 360, where this ornithine decarboxylase reaction-directing residue is substituted by a valine [28].
• METHODS: PPARgamma, ODC and SSAT mRNA levels were evaluated by reverse transcriptase and real-time PCR [29].
• As proof of concept, the ODC/AZ system was used to ablate expression of specific endogenous proteins (e.g., TRAF6; Rb), and was shown to create the expected lesions in cellular pathways that require these proteins [30].
• AZ1 binds to ODC with about a 3-fold higher potency than AZ2, but this cannot account for their distinct degradative activities [31].

Analytical, diagnostic and therapeutic context of ODC1

• The first is the previously described soluble pool, and the second is enriched in phospho-ODC and associated with insoluble cellular material that by immunohistochemistry appears to be organized in conjunction with the keratin cytoskeleton [32].
• Fractionation and ODC immunoprecipitation from [(32)P]orthophosphate-labeled NHEK lysates showed that a phosphorylated form of ODC was present in the insoluble fractions [32].
• Confocal immunofluorescence showed that ODC distribution in NHEK was primarily perinuclear; upon disruption of the actin cytoskeleton with cytochalasin D, ODC distribution was diffuse [32].
• The partial cDNA sequence is 86% homologous to the mouse ODC cDNA, and Northern blots indicate that the human and mouse mRNA species are similar in size [33].
• ODC mRNA was elevated 5-fold in MDA-MB-231 cells versus MCF-7 cells when analyzed in cell culture [34].

References