title: Down regulation of c-Myc and induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU in human colon cancer KM12C cells.
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.
authors.affiliation: Department of Molecular Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, Kagoshima, Japan.
authors.forename: Hong-Ye
authors.initials: HY
authors.lastname: Zhao
authors.forename: Akio
authors.initials: A
authors.lastname: Ooyama
authors.forename: Masatatsu
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Ryuji
authors.initials: R
authors.lastname: Ikeda
authors.forename: Misako
authors.initials: M
authors.lastname: Haraguchi
authors.forename: Sho
authors.initials: S
authors.lastname: Tabata
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Furukawa
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Che
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Iwashita
authors.forename: Toshinori
authors.initials: T
authors.lastname: Oka
authors.forename: Masakazu
authors.initials: M
authors.lastname: Fukushima
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ono
authors.forename: Michihiko
authors.initials: M
authors.lastname: Kuwano
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Akiyama
mesh_terms: D020533:Angiogenesis Inhibitors / Q000235:genetics*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015536:Down-Regulation; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D019700:Thrombospondin 1 / Q000235:genetics*
chemical_list: D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D019700:Thrombospondin 1; D005472:Fluorouracil