Pharmacogenomic profiling and pathway analyses identify MAPK-dependent migration as an acute response to SN38 in p53 null and p53-mutant colorectal cancer cells.

ABSTRACT: The topoisomerase I inhibitor irinotecan is used to treat advanced colorectal cancer and has been shown to have p53-independent anticancer activity. The aim of this study was to identify the p53-independent signaling mechanisms activated by irinotecan. Transcriptional profiling of isogenic HCT116 p53 wild-type and p53 null cells was carried out following treatment with the active metabolite of irinotecan, SN38. Unsupervised analysis methods showed that p53 status had a highly significant impact on gene expression changes in response to SN38. Pathway analysis indicated that pathways involved in cell motility [adherens junction, focal adhesion, mitogen-activated protein kinase (MAPK), and regulation of the actin cytoskeleton] were significantly activated in p53 null cells, but not p53 wild-t

SUBMITTER: Allen WL 

PROVIDER: S-EPMC3428848 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature