A novel variant of ileal bile acid binding protein is up-regulated through nuclear factor-kappaB activation in colorectal adenocarcinoma.
Ileal bile acid binding protein (IBABP) is the only cytosolic protein known to bind and transport bile acids. Because IBABP is reportedly up-regulated in colorectal cancer, it has been suggested as a link between bile acids and the risk of colorectal cancer. However, in this study, we show that IBABP is not up-regulated. Rather, a novel transcript of the IBABP gene, which encodes an additional 49 NH(2)-terminal amino acid residues, is up-regulated in colorectal cancer (P < 0.001). The novel transcript, called IBABP-L, is also distinct from IBABP because its transcription is controlled by nuclear factor-kappaB (NF-kappaB) rather than by the farnesoid X receptor. Most significantly, IBABP-L is necessary for the survival of HCT116 colon cancer cells in the presence of physiologic levels of the secondary bile acid deoxycholate. Collectively, the studies point toward a unique bile acid response pathway involving NF-kappaB and IBABP-L that could be useful for diagnosis and could potentially be targeted for therapeutic benefit.
Fang
Changming
C
Cancer Research Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA.
Dean
Jarrod
J
Smith
Jeffrey W
JW
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003840:Deoxycholic Acid / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D014158:Transcription, Genetic; D015854:Up-Regulation; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
D002635:Chenodeoxycholic Acid; D003840:Deoxycholic Acid; D006913:Hydroxysteroid Dehydrogenases; D016328:NF-kappa B; D020033:Protein Isoforms; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)