α-1抗胰蛋白酶缺失:遗传性肝脏疾病导致肝细胞癌的一种新范例

作     者：Rudnick D.A. Perlmutter D.H. 李翔 

作者机构：University of Pittsburgh School of Medicine Children’ s Hospital of Pittsburgh Department of Pediatrics 3705 Fifth Avenue Pittsburgh PA 15213 United States Dr. 

出 版 物：《世界核心医学期刊文摘（胃肠病学分册）》 (Core Journals in Gastroenterology)

年 卷 期：2006年第2卷第1期

页      面：39-40页

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 100214[医学-肿瘤学] 10[医学] 

主　　题：肝脏疾病 抗胰蛋白酶 肝细胞癌 肝脏损伤 信号转导途径 基因表型 酶激活 球状体 变异程度 遗传修饰 

摘      要：Liver disease in alpha-1-antitrypsin (α 1AT) deficiency is caused by a gain-of-toxic function mechanism engendered by the accumulation of a mutant glycoprotein in the endoplasmic reticulum (ER). The extraordinary degree of variation in phenotypical expression of this liver disease is believed to be determined by genetic modifiers and/or environmental factors that influence the intracellular disposal of the mutant glycoprotein or the signal transduction pathways that are activated. Recent investigations suggest that a specific repertoire of signaling pathways are involved, including the autophagic response, mitochondrial-and ER-caspase activation, and nuclear factor kappa B (NFκ B) activation. Whether activation of these signaling pathways, presumably to protect the cell, inadvertently contributes to liver injury or perhaps protects the cell from one injury and, in so doing, predisposes it to another type of injury, such as hepatocarcinogenesis, is not yet known. Recent studies also suggest that hepatocytes with marked accumulation of α 1ATZ, globule-containing hepatocytes, engender a cancer-prone state by surviving with intrinsic damage and by chronically stimulating in‘ trans’ adjacent relatively undamaged hepatocytes that have a selective proliferative advantage. Further, this paradigm may apply to other genetic and infectious liver diseases that are predisposed to hepatocellular carcinoma.