Induction of epithelial differentiation and DNA demethylation in hamster malignant oral keratinocyte by ornithine decarboxylase antizyme

Takanori Tsuji, Satomi Usui, Tadateru Aida, Tetsuhiko Tachikawa, Guo Fu Hu, Akira Sasaki, Tomohiro Matsumura, Randy Todd, David T.W. Wong

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)24-33
Number of pages10
JournalOncogene
Volume20
Issue number1
DOIs
Publication statusPublished - Jan 4 2001

Keywords

  • DNA demethylation
  • Differentiation
  • Hamster
  • Oral cancer
  • Ornithine decarboxylase antizyme

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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