A novel variant of ileal bile acid binding protein is up-regulated through nuclear factor-κB activation in colorectal adenocarcinorna
A novel variant of ileal bile acid binding protein is up-regulated through nuclear factor-κB activation in colorectal adenocarcinorna
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DOI：
10.1158/0008-5472.can-06-3690
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发表时间：
2007-10-01
期刊：
影响因子：
11.2
通讯作者：
Smith, Jeffrey W.
中科院分区：
文献类型：
--
作者：
Fang, Changming;Dean, Jarrod;Smith, Jeffrey W.
回肠胆汁酸结合蛋白(IBABP)是目前已知的唯一能结合和转运胆汁酸的胞浆蛋白。因为据报道IBABP在结直肠癌中表达上调，它被认为是胆汁酸和结直肠癌风险之间的联系。然而，在这项研究中，我们发现IBABP没有上调。相反，IBABBP基因的一个新的转录本，编码另外49个氨基末端氨基酸残基，在结直肠癌中上调(P<；0.001)。这个新的转录本被称为IBABP-L，也不同于IBABP，因为它的转录是由核因子-kappaB(NF-kappa B)控制的，而不是由法尼类X受体控制的。最值得注意的是，在生理水平的次级胆汁酸脱氧胆酸存在下，IBABBP-L是HCT116结肠癌细胞存活所必需的。总之，这些研究指向了一种涉及核因子-kappaB和IBABP-L的独特胆汁酸反应途径，该途径可能对诊断有用，并可能成为治疗的靶点。
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-kappa B (NF-kappa 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-kappa B and IBABP-L that could be useful for diagnosis and could potentially be targeted for therapeutic benefit.