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聚(ADP - 核糖)聚合酶基因表达状态与人类乳腺癌中的基因组不稳定性

Poly(ADP-ribose) polymerase gene expression status and genomic instability in human breast cancer.

作者信息

Bièche I, de Murcia G, Lidereau R

机构信息

Laboratoire d'Oncogénétique, Centre René Huguenin, 35 rue Dailly, F-92211 St-Cloud, and Ecole Supérieure de Biotechnologie de Strasbourg, UPR 9003 France.

出版信息

Clin Cancer Res. 1996 Jul;2(7):1163-7.

PMID:9816283
Abstract

The poly(ADP-ribose) polymerase gene is involved in DNA repair, cell proliferation, differentiation, and malignant transformation. Because dysregulation of PARP expression might lead to genetic instability in human tumors, we examined PARP gene expression and genetic instability in 35 primary human breast carcinomas. Genetic instability was studied by analyzing nine genetic abnormalities among those most frequently observed in breast tumor DNA, including amplification of proto-oncogenes MYC and ERBB2 and chromosome regions 7p, 11q13, and 20q13, and loss of heterozygosity on chromosome arms 1p, 3p, 7p, 7q, and 11p. We found a significant link between strong PARP gene overexpression and low genetic instability (chi2corr. = 5.33; P = 0.012), pointing to a possible involvement of this gene in DNA repair in human breast tumor cells. A trend toward a link between PARP gene overexpression and amplification at 1q41-q44 (the site of the PARP gene) was also observed, suggesting that dysregulation of PARP expression could be due partly to a gene dosage effect.

摘要

聚(ADP - 核糖)聚合酶基因参与DNA修复、细胞增殖、分化及恶性转化。由于PARP表达失调可能导致人类肿瘤中的基因不稳定,我们检测了35例原发性人类乳腺癌中的PARP基因表达及基因不稳定情况。通过分析在乳腺肿瘤DNA中最常观察到的9种基因异常来研究基因不稳定,这些异常包括原癌基因MYC和ERBB2以及染色体区域7p、11q13和20q13的扩增,以及染色体臂1p、3p、7p、7q和11p上的杂合性缺失。我们发现PARP基因的强过表达与低基因不稳定之间存在显著关联(校正卡方值 = 5.33;P = 0.012),这表明该基因可能参与人类乳腺肿瘤细胞的DNA修复。还观察到PARP基因过表达与1q41 - q44(PARP基因所在位点)扩增之间存在关联趋势,提示PARP表达失调可能部分归因于基因剂量效应。

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