Vander Borght Sara, Libbrecht Louis, Katoonizadeh Aezam, van Pelt Jos, Cassiman David, Nevens Frederik, Van Lommel Alfons, Petersen Bryon E, Fevery Johan, Jansen Peter L, Roskams Tania A
Laboratory of Morphology and Molecular Pathology, University Hospitals Leuven, Belgium.
J Histochem Cytochem. 2006 Sep;54(9):1051-9. doi: 10.1369/jhc.5A6912.2006. Epub 2006 May 18.
Breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette transport protein that is expressed in several organs including the liver. Previous studies have shown that ABC transport proteins play an important pathophysiological role in several liver diseases. However, to date, expression pattern and possible role of BCRP in human liver diseases and animal models have not been studied in detail. Here we investigated the expression pattern of BCRP in normal liver, chronic parenchymal and biliary human liver diseases, and parallel in different rat models of liver diseases. Expression was studied by immunohistochemistry and additionally by RT-PCR analysis in Thy-1-positive rat oval cells. Bile ducts, hepatic progenitor cells, reactive bile ductules, and blood vessel endothelium were immunoreactive for BCRP in normal liver and all types of human liver diseases and in rat models. BCRP was expressed by the canalicular membrane of hepatocytes in normal and diseased human liver, but never in rat liver. Remarkably, there was also expression of BCRP at the basolateral pole of human hepatocytes, and this was most pronounced in chronic biliary diseases. In conclusion, BCRP positivity in the progenitor cells/reactive ductules could contribute to the resistance of these cells to cytotoxic agents and xenotoxins. Basolateral hepatocytic expression in chronic biliary diseases may be an adaptive mechanism to pump bile constituents back into the sinusoidal blood. Strong differences between human and rat liver must be taken into account in future studies with animal models.
乳腺癌耐药蛋白（BCRP/ABCG2）是一种ATP结合盒转运蛋白，在包括肝脏在内的多个器官中表达。先前的研究表明，ABC转运蛋白在几种肝脏疾病中发挥着重要的病理生理作用。然而，迄今为止，BCRP在人类肝脏疾病和动物模型中的表达模式及可能的作用尚未得到详细研究。在此，我们研究了BCRP在正常肝脏、慢性实质性和胆汁性人类肝脏疾病中的表达模式，并在不同的大鼠肝脏疾病模型中进行了平行研究。通过免疫组织化学进行表达研究，并在Thy-1阳性大鼠卵圆细胞中另外通过RT-PCR分析进行研究。在正常肝脏、所有类型的人类肝脏疾病以及大鼠模型中，胆管、肝祖细胞、反应性胆小管和血管内皮对BCRP呈免疫反应性。在正常和患病的人类肝脏中，BCRP由肝细胞的胆小管膜表达，但在大鼠肝脏中从未表达。值得注意的是，在人类肝细胞的基底外侧极也有BCRP表达，这在慢性胆汁性疾病中最为明显。总之，祖细胞/反应性胆小管中的BCRP阳性可能有助于这些细胞对细胞毒性剂和外源性毒素的抵抗。慢性胆汁性疾病中肝细胞基底外侧的表达可能是一种将胆汁成分泵回窦状血液的适应性机制。在未来的动物模型研究中，必须考虑人类和大鼠肝脏之间的强烈差异。
