PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells
Braz. j. med. biol. res
;
48(3): 226-233, 03/2015. graf
Artigo
em Inglês
| LILACS
| ID: lil-741251
ABSTRACT
Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.
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Índice:
LILACS (Américas)
Assunto principal:
Asma
/
Genes MHC Classe I
/
Exposição Ocupacional
/
Genes MHC da Classe II
/
Isocianatos
/
Doenças Profissionais
Tipo de estudo:
Ensaio Clínico Controlado
/
Estudo de etiologia
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Fatores de risco
Limite:
Adulto
/
Feminino
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Braz. j. med. biol. res
Assunto da revista:
Biologia
/
Medicina
Ano de publicação:
2015
Tipo de documento:
Artigo
País de afiliação:
Coréia do Sul
Instituição/País de afiliação:
Chonbuk National University Hospital/KR
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