Butyrate induced changes in Wnt-signaling specific gene expression in colorectal cancer cells.

ABSTRACT: BACKGROUND: We have determined that butyrate, which is derived from the fermentation of dietary fiber in the colonic lumen, hyperactivates Wnt activity in colorectal (CRC) cells, and that this upregulation of Wnt signaling is causatively related to the induction of apoptosis. To better understand the genetic program regulated by butyrate-mediated Wnt hyperactivation, we performed total human genome microarray analyses on HCT-116 CRC cells in the presence or absence of a physiologically relevant concentration of butyrate. To evaluate changes in Wnt-specific gene expression, Wnt activity was suppressed with inducible dominant negative Tcf4 (DN-Tcf4). Six biological replicates of a full human genome microarray were performed, and the data deposited into the Gene Expression Omnibus database, according to Minimum Information About A Microarray Experiment standards. RESULTS: Reporter assay and western blot data confirm that DN-Tcf4 is expressed at high levels in stably transfected HCT-116 cells upon cotreatment with doxycycline and butyrate, and that these cells exhibit a marked repression of butyrate-mediated Wnt hyperactivation. Analysis of six biological replicates of microarray analyses indicated that 1008 genes are modulated by butyrate (>two-fold, P?

SUBMITTER: Lazarova DL 

PROVIDER: S-EPMC4022274 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature