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A Novel Variant of Ileal Bile Acid Binding Protein Is Up-regulated through Nuclear Factor-B Activation in Colorectal Adenocarcinoma

Cancer Research Center, Burnham Institute for Medical Research, La Jolla, California

Requests for reprints: Jeffrey W. Smith, Cancer Research Center, Burnham Institute for Medical Research, La Jolla, CA 92037. Phone: 858-646-3121; Fax: 858-795-5221; E-mail: jsmith{at}burnham.org.

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 NH₂-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-B (NF-B) 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-B and IBABP-L that could be useful for diagnosis and could potentially be targeted for therapeutic benefit. [Cancer Res 2007;67(19):9039–46]