Overexpression of poly(ADP-ribose) polymerase-1 (PARP-1) in the early stage of colorectal carcinogenesis
Overexpression of poly(ADP-ribose) polymerase-1 (PARP-1) in the early stage of colorectal carcinogenesis
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DOI：
10.1016/j.ejca.2006.01.061
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发表时间：
2006-09-01
影响因子：
8.4
通讯作者：
Shinomura, Yasuhisa
中科院分区：
文献类型：
--
作者：
Nosho, Katsuhiko;Yamamoto, Hiroyuki;Shinomura, Yasuhisa
结直肠癌的发生主要是由APC或β -连环蛋白（CTNNB1）基因突变引起的Wnt信号通路异常激活引发的。聚（adp -核糖）聚合酶-1 （PARP-1）是一种高度保守的核酶，与DNA紧密结合，在DNA修复、重组、增殖和基因组稳定中发挥作用。最近有研究表明，PARP-1是TCF-4/ β -连环蛋白诱发的基因转激活的一种新的共激活因子，可能在结直肠癌的发生中发挥作用。本研究的目的是检测PARP-1在散发性结直肠癌早期的表达，并确定其是否与a-catenin及其靶基因c-myc、cyclin D1、基质金属蛋白酶（matrix metalloproteinase， MMP）-7的表达相关。采用半定量逆转录聚合酶链反应（RT-PCR）对91例结直肠肿瘤（包括65例腺瘤和26例粘膜下癌）进行了PARP-1、β -连环蛋白、c-myc、cyclin D1和MMP-7的表达分析。免疫组织化学分析PARP-1和β -连环蛋白。91例肿瘤中64例（70.3%）存在PARP-1 mRNA过表达。PARP-1过表达与肿瘤大小和组织病理学有显著相关性。91例肿瘤中β -catenin、c-myc、cyclin D1和MMP-7 mRNA的过表达率分别为39.6%、78.0%、83.5%和72.5%。PARP-1过表达与β -catenin、c-myc、cyclin D1、MMP-7过表达显著相关。免疫组织化学也证实了PARP-1表达与β -连环蛋白过表达的相关性。结果提示PARP-1与p-catenin、c-myc、cyclin D1、MMP-7共同参与结直肠癌的早期发生。(c) 2006 Elsevier Ltd.版权所有。
Colorectal carcinogenesis is initiated mainly by aberrant activation of the Wnt signaling pathway, caused by mutation of either APC or beta-catenin (CTNNB1) gene. Poly(ADP-ribose) polymerase-1 (PARP-1) is a highly conserved nuclear enzyme, which binds tightly to DNA and plays a role in DNA repair, recombination, proliferation and genomic stability. It has recently been shown that PARP-1 is a novel co-activator of TCF-4/beta-catenin-evoked gene transactivation and may play a role in colorectal carcinogenesis. The aim of this study was to examine the PARP-1 expression and determine whether it is correlated with the expression of a-catenin and its target genes such as c-myc, cyclin D1 and matrix metalloproteinase (MMP)-7 in the early stage of sporadic colorectal carcinogenesis. Using the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), 91 colorectal tumours, including 65 adenomas and 26 submucosal (pT1) cancers, were analysed for the expression of PARP-1, beta-catenin, c-myc, cyclin D1 and MMP-7. Immunohistochemical analysis of PARP-1 and beta-catenin was also performed. PARP-1 mRNA overexpression was detected in 64 (70.3%) of the 91 tumours. PARP-1 overexpression was significantly correlated with tumour size and histopathology. Overexpression of beta-catenin, c-myc, cyclin D1 and MMP-7 mRNA expression was observed in 39.6%, 78.0%, 83.5% and 72.5% of the 91 tumours, respectively. PARP-1 overexpression was correlated significantly with overexpression of beta-catenin, c-myc, cyclin D1 and MMP-7. Correlation of PARP-1 expression with beta-catenin overexpression was also demonstrated by immunohistochemistry. The results suggest that PARP-1, in conjunction with p-catenin, c-myc, cyclin D1 and MMP-7, plays an important role in the early stage of colorectal carcinogenesis. (c) 2006 Elsevier Ltd. All rights reserved.