Retinoic acid (RA) receptor transcriptional activation correlates with inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase (ODC) activity by retinoids: A potential role for trans-RA-induced ZBP-89 in ODC inhibition

Marcia I. Dawson, Ju Hui Park, Guo Quan Chen, Wan Ru Chao, Linda Dousman, Nahid Waleh, Peter D. Hobbs, Ling Jong, Lawrence Toll, Xiao Kun Zhang, Jian Gu, Anissa Agadir, Juanita L. Merchant, Longchuan Bai, Ajit K. Verma, Scott M. Thacher, Roshantha A.S. Chandraratna, Braham Shroot, Donald L. Hill

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Evaluation of retinoic acid receptor (RAR) subtype-selective α and γ agonists and antagonists and a retinoid X receptor (RXR) class-selective agonist for efficacy at inhibiting both induction of ornithine decarboxylase (ODC) by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse epidermis and rat tracheal epithelial cells and the appearance of papillomas in mouse epidermis treated in the 2-stage tumor initiation-promotion model indicated that (i) RXR class-selective transcriptional agonists, such as MMII246, were not involved in ODC inhibition; (ii) RAR-selective agonists that induce gene transcription from RAresponsive elements (RAREs) were active at low concentrations; (iii) RAR-selective antagonists that bind RARs and inhibit AP-I activation on the collagenase promoter but do not activate RAREs to induce gene transcription were less effective inhibitors; and (iv) RARγ-selective retinoid agonists were more effective inhibitors of TPA-induced ODC activity than RARα-selective agonists. These results suggest that RARE activation has a more important role in inhibition of ODC activity than RXR activation or AP-I inhibition and that RARγ-selective agonists would be the most useful inhibitors of epithelial cell proliferation induced by tumor promoters. The natural retinoid all-trans-RA induced expression of transcription factor ZBP-89, which represses activation of the GC box in the ODC promoter by the transcription factor SpI. (C) 2001 WiIey-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)8-21
Number of pages14
JournalInternational Journal of Cancer
Volume91
Issue number1
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • Ornithine decarboxylase
  • Retinoic acid receptor
  • Retinoid
  • Tumor promotion
  • ZBP-89 expression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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