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Peroxisome proliferator‐activated receptor γ‐dependent and ‐independent growth inhibition of gastrointestinal tumour cells
Author(s) -
Rumi M. Azharul Karim,
Ishihara Shunji,
Kadowaki Yasunori,
OrtegaCava C. F.,
Kazumori Hideaki,
Kawashima Kousaku,
Yoshino Nagisa,
Yuki Takafumi,
Ishimura Norihisa,
Kinoshita Yoshikazu
Publication year - 2004
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2004.00793.x
Subject(s) - troglitazone , peroxisome proliferator activated receptor , thiazolidinedione , biology , rosiglitazone , growth inhibition , transcription factor , cell growth , receptor , cell culture , microbiology and biotechnology , cancer research , endocrinology , biochemistry , gene , genetics , type 2 diabetes , diabetes mellitus
Peroxisome proliferator‐activated receptor γ (PPARγ) acts as a ligand‐activated transcription factor. Although ligand‐induced cellular differentiation and growth inhibition have been mostly studied on human cancers expressing PPARγ, it is unclear if the transcriptional activation of PPARγ is the main mechanism of growth inhibition. In this study, we investigated whether there is a link between growth inhibitory effect and transcriptional activation of PPARγ in several gastrointestinal tumour cell lines. The transcriptional activation potential of PPARγ was assessed by reporter gene assay employing a PPRE‐luciferase vector, and growth inhibitory effect of PPARγ was investigated by 3 H‐thymidine incorporation assay, in the presence or absence of thiazolidinedione ligands, rosiglitazone and troglitazone. As expected, in the case of cell lines positive for the transcriptional activation potential of PPARγ (T.Tn, MKN‐45 and LoVo), both the ligands induced growth inhibition. However, in case of some other cell lines negative for the transcriptional activation potential of PPARγ (TT, AGS and HCT‐15), troglitazone still showed a growth inhibitory effect. Administration of the PPARγ antagonist GW9662 did not reverse this growth inhibitory activity of troglitazone. The introduction of dominant negative mutants of PPARγ did not suppress the activity either. These observations suggest that while rosiglitazone inhibits cellular growth predominantly through transcriptional activation of PPARγ, troglitazone can induce it both in PPARγ‐dependent and ‐independent pathways.