在肝硬化患者的人类肝细胞癌中，增殖细胞核抗原（PCNA）参与细胞增殖，并在DNA修复过程中与P21协同作用。

In human hepatocellular carcinoma in cirrhosis proliferating cell nuclear antigen (PCNA) is involved in cell proliferation and cooperates with P21 in DNA repair.

作者信息

Gramantieri Laura, Trerè Davide, Chieco Pasquale, Lacchini Michela, Giovannini Catia, Piscaglia Fabio, Cavallari Antonino, Bolondi Luigi

机构信息

Center for Applied Biomedical Research (CRBA), University of Bologna and St. Orsola-Malpighi University Hospital, Bologna, Italy.

出版信息

J Hepatol. 2003 Dec;39(6):997-1003. doi: 10.1016/s0168-8278(03)00458-6.

DOI:10.1016/s0168-8278(03)00458-6

PMID:14642618

Abstract

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 cirrhosis 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.

摘要

背景

增殖细胞核抗原（PCNA）是一种参与DNA合成与修复的核蛋白。在DNA合成与修复过程中，唯一具有活性的PCNA部分紧密结合于DNA。同样，在DNA修复过程中，一部分p21以去污剂不溶性形式与PCNA共定位。

目的

本研究旨在分析与DNA结合的PCNA和p21的存在在多大程度上与肝细胞癌（HCC）中的细胞增殖和DNA修复相关。

方法

对26例HCC及其周围的肝硬化组织进行研究。通过免疫印迹分析PCNA和p21与DNA结合及可溶于去污剂的部分。通过免疫细胞化学评估p53和Ki67标记指数（Ki67-LI）。

结果

在所有样本中均发现了PCNA和p21的可溶部分。26例肝硬化样本中有1例显示出与DNA结合的PCNA部分，而没有病例表达与DNA结合的p21。14例HCC显示出与DNA结合的PCNA部分。在Ki67-LI与与DNA结合的PCNA之间发现了高度显著的相关性，但与可溶于去污剂的PCNA无关。在这14例HCC中的6例中存在与DNA结合的p21和PCNA，表明存在持续的DNA修复活性，并且与高组织学分级和高Ki67-LI相关。