Molecular pharmacology
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Molecular pharmacology · Nov 2005
15-deoxy-Delta12,14 prostaglandin J2 up-regulates Kruppel-like factor 4 expression independently of peroxisome proliferator-activated receptor gamma by activating the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signal transduction pathway in HT-29 colon cancer cells.
15-Deoxy-Delta(12,14) prostaglandin J2 (15d-PGJ2) is a natural ligand for the peroxisome proliferator-activated receptor gamma (PPARgamma) that exhibits antiproliferative activity in colon cancer cells, but its mechanism of action is still poorly understood. In this study, we showed that Krüppel-like factor 4 (KLF4) is one of the downstream effectors of 15d-PGJ2. Treatment of HT-29 cells with 15d-PGJ2 resulted in up-regulation of both KLF4 mRNA and protein expression, and these increases were also observed in other colon cancer cell lines. ⋯ Furthermore, KLF4 induction by 15d-PGJ2 occurred only in signal transducer and activator of transcription 1 (STAT1)-expressing, not in STAT1-knockout cells. Together, these results suggest that 15d-PGJ2-induced growth inhibition of colon cancer cells is mediated, at least in part, through up-regulation of KLF4 expression. This induction is unlikely to be mediated through the PPARgamma receptor but may involve the mitogen-activated protein kinase kinase/ERK pathway and is STAT1-dependent.