Aberrant expression of fetal RNA-binding protein p62 in liver cancer and liver cirrhosis
Aberrant expression of fetal RNA-binding protein p62 in liver cancer and liver cirrhosis
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DOI：
10.1016/s0002-9440(10)61770-1
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发表时间：
2001-09-01
影响因子：
6
通讯作者：
Tan, EM
中科院分区：
文献类型：
--
作者：
Lu, ML;Nakamura, RM;Tan, EM
p62是一种RNA结合蛋白，通过用来自肝细胞癌（HCC）患者的自身抗体对cDNA表达文库进行免疫筛选而分离得到。这种自身抗原与编码胰岛素样生长因子II的mRNA结合，胰岛素样生长因子II已被发现在HCC中过度表达，并且在转基因动物中具有致瘤性。对HCC肝脏的免疫组织化学分析显示，33%（27例中的9例）在癌结节中所有恶性细胞的细胞质中呈现出容易检测到的p62蛋白染色，而在相邻的非恶性肝细胞中则检测不到。此外，两名胆管癌患者中有一名在恶性胆管上皮细胞中表达p62。与HCC结节中所有细胞均匀表达相反，在肝硬化结节中的散在细胞中也检测到p62表达。在HCC结节中，通过逆转录酶 - 聚合酶链反应分析也检测到p62 mRNA。9例正常成人肝脏不含有可检测到的p62 mRNA或p62蛋白，而5例胎儿肝脏的mRNA和蛋白均为阳性。这些观察结果表明，p62受发育调控，在胎儿肝脏中表达，但在成人肝脏中不表达，在HCC中异常表达，并且可能通过调节胰岛素样生长因子II等生长因子的表达在HCC和肝硬化中的异常细胞增殖中起作用。
p62 is a RNA-binding protein that was isolated by immunoscreening a cDNA expression library with autoantibodies from patients with hepatocellular carcinoma (HCC). This autoantigen binds to mRNA encoding insulin-like growth factor II, which has been found to be overexpressed in HCC and is tumorigenic in transgenic animals. Immunohistochemical analysis of HCC liver showed that 33% (9 of 27) exhibited readily detectable staining of p62 protein in the cytoplasm of all malignant cells in cancer nodules, whereas it was undetectable in adjacent nonmalignant liver cells. In addition one of two patients with cholangiocarcinoma expressed p62 in malignant bile duct epithelial cells. p62 expression was also detected in scattered cells in cirrhotic nodules in contrast to uniform expression in all cells in HCC nodules. In HCC nodules, p62 mRNA was also detected by reverse transcriptase-polymerase chain reaction analysis. Nine normal adult livers did not contain detectable p62 mRNA or p62 protein whereas five fetal livers were all positive for mRNA and protein. The observations show that p62 is developmentally regulated, expressed in fetal, but not in adult liver, and aberrantly expressed in HCC and could be playing a role in abnormal cell proliferation in HCC and cirrhosis by modulating expression of growth factors such as insulin-like growth factor II.