西亞試劑：Peroxisome proliferator-activated receptor γ agonists induc

Peroxisome proliferator-activated receptor γ agonists induce cell cycle arrest through transcriptional regulation of Kruppel-like factor 4

Sheng Li, Qibing Zhou, Huan He, Yahui Zhao and Zhihua Liu*

Peroxisome proliferator activated receptor γ (PPARγ), a subgroup of ligand-activated nuclear receptors, plays critical roles in cell cycle regulation, differentiation, apoptosis and invasion. PPARγ is involved in tumorigenesis and is a potent target for cancer therapy. PPARγ transactivation of KLF4 has been demonstrated in various studies; however, how PPARγ regulates KLF4 expression is not clear. In this study, we revealed that PPARγ regulates the expression of KLF4 by binding directly to the PPAR response element (PPRE) within the KLF4 promoter. The PPRE resided at -1657bp to -1669bp upstream of the KLF4 ATG codon, which is essential for the transactivation of TGZ-induced KLF4 expression. Furthermore, we found that stable silencing of KLF4 obviously suppressed the G1/S arrest and anti-proliferation effects induced by PPARγ ligands. Taken together, our data indicated that upregulating KLF4 upon PPARγ activation is mediated through PPRE in KLF4 promoter, thus providing further insights into PPARγ signal transduction pathway as well as a novel cancer therapeutic strategy

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