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  • Title: Thiazolidinediones inhibit REG Ialpha gene transcription in gastrointestinal cancer cells.
    Author: Yamauchi A, Takahashi I, Takasawa S, Nata K, Noguchi N, Ikeda T, Yoshikawa T, Shervani NJ, Suzuki I, Uruno A, Unno M, Okamoto H, Sugawara A.
    Journal: Biochem Biophys Res Commun; 2009 Feb 13; 379(3):743-8. PubMed ID: 19118520.
    Abstract:
    REG (Regenerating gene) Ialpha 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 PPARgamma-agonist thiazolidinediones (TZDs) inhibited cell proliferation and REG Ialpha protein/mRNA expression in gastrointestinal cancer cells. TZDs inhibited the REG Ialpha gene promoter activity, via its cis-acting element which lacked PPAR response element and could not bind to PPARgamma, in PPARgamma-expressing gastrointestinal cancer cells. The inhibition was reversed by co-treatment with a specific PPARgamma-antagonist GW9662. Although TZDs did not inhibit the REG Ialpha gene promoter activity in PPARgamma-non-expressing cells, PPARgamma overexpression in the cells recovered their inhibitory effect. Taken together, TZDs inhibit REG Ialpha gene transcription through a PPARgamma-dependent pathway. The TZD-induced REG Ialpha 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 Ialpha and PPARgamma.
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