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Thiazolidinediones inhibit REG Ialpha gene transcription in gastrointestinal cancer cells.

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

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

doi

10.1016/j.bbrc.2008.12.113

subject

Has Abstract

pub_date

2009-02-13 00:00:00

pages

743-8

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(08)02538-2

journal_volume

379

pub_type

杂志文章

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