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.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Zhao HY,Ooyama A,Yamamoto M,Ikeda R,Haraguchi M,Tabata S,Furukawa T,Che XF,Iwashita K,Oka T,Fukushima M,Nakagawa M,Ono M,Kuwano M,Akiyama Sdoi
10.1016/j.canlet.2008.04.045subject
Has Abstractpub_date
2008-10-18 00:00:00pages
156-63issue
1eissn
0304-3835issn
1872-7980pii
S0304-3835(08)00357-1journal_volume
270pub_type
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