Title of article :
Down regulation of c-Myc and induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU in human colon cancer KM12C cells
Author/Authors :
Zhao، نويسنده , , Hong-Ye and Ooyama، نويسنده , , Akio and Yamamoto، نويسنده , , Masatatsu and Ikeda، نويسنده , , Ryuji and Haraguchi، نويسنده , , Misako and Tabata، نويسنده , , Sho and Furukawa، نويسنده , , Tatsuhiko and Che، نويسنده , , Xiao-Fang and Iwashita، نويسنده , , Ken-ichi and Oka، نويسنده , , Toshinori and Fukushima، نويسنده , , Masakazu and Nakagawa، نويسنده , , Masayuki and Ono، نويسنده , , Mayumi and Kuwano، نويسنده , , Michihiko and Akiyama، نويسنده , , Shin-ichi، نويسنده ,
Abstract :
5-FU is commonly used for treatment of various solid tumors including colon carcinoma. We have previously demonstrated that Egr-1 induced by 5-FU enhanced TSP-1 expression in human colon cancer KM12C cells. In this study, a Genechip analysis of KM12C cells treated with 5-FU revealed down-regulation of 924 genes and up-regulation of 460 genes. The decreased expression of c-Myc mRNA and phosphorylated c-Myc were detected and confirmed by RT-PCR and immunoblotting. Since 5-FU induced the expression of TSP-1, we examined the effect of c-Myc on the TSP-1 promoter. Deletion of the TSP-1 promoter region in which binding sites for c-Myc reside had no effect on the TSP-1 promoter activity induced by 5-FU. Meanwhile, 5-FU dose-dependently decreased the expression of miR-17-92 cluster. These findings suggest that 5-FU decreased the expression of c-Myc and consequently miR-17-92 cluster and increased the expression of TSP-1 mRNA.
Keywords :
c-Myc , Thrombospondin-1 , 5-fluorouracil , Genechip analysis
