The bile acid deoxycholic acid (DCA) at neutral pH, activates NF-κB and induces IL-8 expression in oesophageal cells in vitro

摘要: Barrett's oesophagus patients accumulate chromosomal defects during the histological progression to cancer, one of most prominent which is amplification whole chromosome 4. We aimed study role that transcription factor NF-kappaB, a candidate cancer- promoting gene, present on 4, plays in oesophagus, using OE33 cells as model. Specifically, we wanted determine if NF-kappaB was activated by exposure bile acid (deoxycholic acid) oesophageal cells. employed pathway specific cDNA microarrays and real-time PCR, first identify induced genes specifically investigate NF-kappaB. An reporter system used, well an inhibitor (pyrrolidine dithiocarbamate) confirm activation bile. show physiological levels DCA (100-300 microM) were capable activating inducing target gene expression (particularly IkappaB IL-8). Other abnormalities also shown be DCA. Importantly, preliminary experiments showed occurred at neutral pH, but not pH. Acidic did however cause over-expression c-myc oncogene, reported previously. Hence, data showing may key mediator carcinogenesis exposed tissues. In addition, acids appear play significant part reflux changes. postulate survival linked previous cytogenetic from our laboratory NF-kappaB's (chromosome 4), cancer progression. Hence 4 provide mechanism for tissues via