TY - JOUR
T1 - Thiazolidinediones inhibit REG Iα gene transcription in gastrointestinal cancer cells
AU - Yamauchi, Akiyo
AU - Takahashi, Iwao
AU - Takasawa, Shin
AU - Nata, Koji
AU - Noguchi, Naoya
AU - Ikeda, Takayuki
AU - Yoshikawa, Takeo
AU - Shervani, Nausheen J.
AU - Suzuki, Iwao
AU - Uruno, Akira
AU - Unno, Michiaki
AU - Okamoto, Hiroshi
AU - Sugawara, Akira
N1 - Funding Information:
This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (Grant No. 16023211).
PY - 2009/2/13
Y1 - 2009/2/13
N2 - 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.
AB - 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.
KW - Gastrointestinal cancer
KW - PPARγ
KW - REG Iα
KW - Thiazolidinedione
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U2 - 10.1016/j.bbrc.2008.12.113
DO - 10.1016/j.bbrc.2008.12.113
M3 - Article
C2 - 19118520
AN - SCOPUS:58549111840
SN - 0006-291X
VL - 379
SP - 743
EP - 748
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -
