Thiazolidinediones inhibit REG Iα gene transcription in gastrointestinal cancer cells

Akiyo Yamauchi, Iwao Takahashi, Shin Takasawa, Koji Nata, Naoya Noguchi, Takayuki Ikeda, Takeo Yoshikawa, Nausheen J. Shervani, Iwao Suzuki, Akira Uruno, Michiaki Unno, Hiroshi Okamoto, Akira Sugawara

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

REG (Regenerating gene) Iα protein functions as a growth factor for gastrointestinal cancer cells, and its mRNA expression is strongly associated with a poor prognosis in gastrointestinal cancer patients. We here demonstrated that PPARγ-agonist thiazolidinediones (TZDs) inhibited cell proliferation and REG Iα protein/mRNA expression in gastrointestinal cancer cells. TZDs inhibited the REG Iα gene promoter activity, via its cis-acting element which lacked PPAR response element and could not bind to PPARγ, in PPARγ-expressing gastrointestinal cancer cells. The inhibition was reversed by co-treatment with a specific PPARγ-antagonist GW9662. Although TZDs did not inhibit the REG Iα gene promoter activity in PPARγ-non-expressing cells, PPARγ overexpression in the cells recovered their inhibitory effect. Taken together, TZDs inhibit REG Iα gene transcription through a PPARγ-dependent pathway. The TZD-induced REG Iα mRNA reduction was abolished by cycloheximide, indicating the necessity of novel protein(s) synthesis. TZDs may therefore be a candidate for novel anti-cancer drugs for patients with gastrointestinal cancer expressing both REG Iα and PPARγ.

Original languageEnglish
Pages (from-to)743-748
Number of pages6
JournalBiochemical and biophysical research communications
Volume379
Issue number3
DOIs
Publication statusPublished - 2009 Feb 13

Keywords

  • Gastrointestinal cancer
  • PPARγ
  • REG Iα
  • Thiazolidinedione

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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