Induction of epithelial differentiation and DNA demethylation in hamster malignant oral keratinocyte by ornithine decarboxylase antizyme
| Autor: | David T.W. Wong, Takanori Tsuji, Tadateru Aida, Tomohiro Matsumura, Tetsuhiko Tachikawa, Akira Sasaki, Randy Todd, Guo-fu Hu, Satomi Usui |
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| Rok vydání: | 2000 |
| Předmět: |
Intracellular Fluid
Keratinocytes Cancer Research S-Adenosylmethionine genetic structures Cellular differentiation Injections Subcutaneous Hamster Mice Nude Antineoplastic Agents Biology Ornithine Decarboxylase Transfection DNA methyltransferase Decarboxylation Ornithine decarboxylase Mice Cricetinae Genetics Biomarkers Tumor Tumor Cells Cultured Animals Dinucleotide Repeats Molecular Biology Ornithine decarboxylase antizyme Gene Expression Profiling fungi Cell Cycle Mouth Mucosa Proteins Cell Differentiation Epithelial Cells DNA Methylation Ornithine Decarboxylase Inhibitors Molecular biology Growth Inhibitors Culture Media Enzyme Activation Agar DNA demethylation Phenotype Protein Biosynthesis DNA methylation Ectopic expression Cell Division |
| Zdroj: | Oncogene. 20(1) |
| ISSN: | 0950-9232 |
| Popis: | The hamster ornithine decarboxylase antizyme (ODC-Az) cDNA was transfected into the hamster malignant oral keratinocyte cell line, HCPC-1. Ectopic expression of ODC-Az resulted in the reversion of malignant phenotypes and alteration of DNA methylation status of CCGG sites. The phenotypes examined include ODC enzymatic activity, doubling time, morphological change, anchorage dependent growth, tumorigenicity in nude mice, induction of epithelial differentiation marker protein (involucrin), and change of cell cycle position. Comparison of CCGG DNA methylation status of the ODC-Az and control vector transfectants revealed a significant increase in demethylation of 5-methyl cytosines (m5C) of CCGG sites in the ODC-Az transfectants. Ectopic expression of ODC-Az gene in hamster malignant oral keratinocytes led to reduce ODC activity and the subsequent demethylation of 5-methyl cytosines, presumably via the ODC/ polyamines/ decarboxylated S-adenosylmethionine (dc-AdoMet) pathways. Our data suggest that ODC-Az shared the same pathway of polyamines/ dc-AdoMet/DNA methyltransferase (DNA MTase). We propose that ODC-Az mediates a novel mechanism in tumor suppression by DNA demethylation and presumably re-activation of key cellular genes silenced by DNA hypermethylation during cancer development. Oncogene (2001) 20, 24 - 33. |
| Databáze: | OpenAIRE |
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