Human homologue of maid is a useful marker protein in hepatocarcinogenesis
Human homologue of maid is a useful marker protein in hepatocarcinogenesis
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DOI：
10.1053/j.gastro.2005.03.014
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发表时间：
2005-05-01
期刊：
影响因子：
29.4
通讯作者：
Okita, K
中科院分区：
文献类型：
--
作者：
Takami, T;Terai, S;Okita, K
背景与目的：Human homologue of maid （HHM）是一种参与肝干细胞发育和分化的螺旋-环-螺旋（HLH）转录调控蛋白。我们分析了HHM在肝癌发生中的潜在作用。方法：我们分析了HHM在大鼠肝癌发生的胆碱缺乏l -氨基酸（CDAA）饮食模型和人腺瘤性增生（AH）和肝细胞癌（HCC）活检样本中的表达。我们评估了HHM对细胞增殖的影响。我们使用酵母2杂交筛选与HHM蛋白结合的蛋白质。结果：HHM在CDAA饮食模型大鼠肝灶及肝细胞癌中均有高表达。32例AH样本中有23例（72%），28例高分化HCC样本中有19例（68%），18例中低分化HCC样本中有9例（50%）表达HHM蛋白。过表达的HHM增强了S期。HHM干扰RNA显著抑制细胞增殖。酵母2杂交筛选发现Jun激活结构域结合蛋白I （Jab1）是HHM的结合伙伴。通过免疫沉淀和免疫荧光组织化学证实HHM与Jab1结合。Jab1在人AH和HCC中均有表达。我们发现HHM和Jabl在AH和HCC组织中的表达水平存在相关性（chi(2)检验P = 0.027）。结论：HHM在肝癌发生的早期就有高水平的表达，提示HHM可能是一种有用的检测标记蛋白。
Background & Aims: Human homologue of maid (HHM) is a helix-loop-helix (HLH) transcriptional regulatory protein that is involved in the hepatic stem cell development and differentiation. We analyzed the potential involvement of HHM in hepatocarcinogenesis. Methods: We analyzed HHM expression in the choline-deficient L-amino acid defined (CDAA) diet model of rat hepatocarcinogenesis and in human adenomatous hyperplasia (AH) and hepatocellular carcinoma (HCC) biopsy samples. We assessed the effects of HHM on cell proliferation. We screened proteins that bind to HHM protein using a yeast 2-hybrid screen. Results: High HHM expression was seen in foci and HCC induced in the rat CDAA diet model. HHM protein was expressed in 23 of 32 AH samples (72%), 19 of 28 well-differentiated HCC samples (68%), and 9 of 18 poorly-moderately differentiated HCC samples (50%). Over-expressed HHM enhanced the S phase. HHM interference RNA significantly inhibited cell proliferation. A yeast 2-hybrid screen identified Jun activation domain-binding protein I (Jab1) as a binding partner for HHM. We confirmed HHM and Jab1 binding by immunoprecipitation and immunofluorescent histochemistry. The expression of Jab1 was found in human AH and HCC samples. We found an association between levels of expression of HHM and those of Jabl in AH and HCC tissues examined (P =.027 by chi(2) test). Conclusions: High-level HHM expression was found from the very early stages of hepatocarcinogenesis, suggesting that HHM may be a useful marker protein to detect.