In human hepatocellular carcinoma in cirrhosis, proliferating cell nuclear antigen (PCNA) is involved in cell proliferation and cooperates with P21 in DNA repair
In human hepatocellular carcinoma in cirrhosis, proliferating cell nuclear antigen (PCNA) is involved in cell proliferation and cooperates with P21 in DNA repair
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DOI：
10.1016/s0168-8278(03)00458-6
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发表时间：
2003-12-01
影响因子：
25.7
通讯作者：
Bolondi, L
中科院分区：
文献类型：
--
作者：
Gramantieri, L;Trerè, D;Bolondi, L
背景：增殖细胞核抗原（PCNA）是一种参与DNA合成和修复的核蛋白。在DNA合成和修复过程中，仅有的活性PCNA部分与DNA紧密结合。同样，在DNA修复过程中，一部分p21与PCNA共定位在洗涤剂不溶性form.Aim：本研究的目的是分析在何种程度上存在的DNA结合的PCNA和p21与细胞增殖和DNA修复在肝细胞癌（HCC）。免疫印迹法分析PCNA和p21的DNA结合和洗涤剂可溶性部分。结果：PCNA和p21蛋白在所有标本中均可见可溶性表达。26例胃癌组织中有1例PCNA阳性，无1例p21阳性。14例HCC显示DNA结合的PCNA分数。Ki 67-LI与DNA结合型PCNA呈高度显著相关，而与洗涤剂可溶型PCNA无显著相关性。DNA结合的p21和PCNA，表明正在进行的DNA修复活动，存在于6这14个肝癌和相关的高组织学分级和高Ki 67-LI。结论：我们的研究结果表明，在肝癌PCNA参与DNA合成和修复，高度增殖的肝癌可能会显示持续的DNA修复。(C)2003年欧洲肝脏研究协会。由Elsevier B. V.出版，版权所有。
Background: Proliferating cell nuclear antigen (PCNA) is a nuclear protein involved in DNA-synthesis and repair. During DNA-synthesis and repair the only active PCNA fraction is tightly bound to DNA. Similarly, during DNA-repair, a fraction of p21 colocalizes with PCNA in a detergent-insoluble form.Aim: The aim of the study was to analyze to what extent the presence of DNA-bound PCNA and p21 correlates with cell proliferation and DNA-repair in hepatocellular carcinoma (HCC).Methods: Twenty-six HCCs and surrounding cirrhotic tissue were studied. The DNA-bound and detergent-soluble fractions of PCNA and p21 were analyzed by immunoblotting. P53 and Ki67-Labeling Index (Ki67-LI) were evaluated by immunocytochemistry.Results: Soluble fractions of PCNA and p21 were found in all samples. One out of 26 cirrhotic samples displayed a DNA-bound fraction of PCNA while no case expressed DNA-bound p21. Fourteen HCCs showed a DNA-bound PCNA fraction. A highly significant correlation was found between Ki67-LI and DNA-bound PCNA but not with detergent-soluble PCNA. DNA-bound p21 and PCNA, indicating ongoing DNA repair activity, were present in 6 of these 14 HCCs and correlated with a high histological grade and high Ki67-LI.Conclusions: Our results suggest that in HCC PCNA participates both in DNA synthesis and repair and that highly proliferating HCCs may display a sustained DNA-repair. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.