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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

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 S

doi

10.1016/j.canlet.2008.04.045

subject

Has Abstract

pub_date

2008-10-18 00:00:00

pages

156-63

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(08)00357-1

journal_volume

270

pub_type

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