Dabholkar M, Bostick-Bruton F, Weber C, Bohr V A, Egwuagu C, Reed E
Medicine Branch, National Cancer Institute, Bethesda, Md. 20892.
J Natl Cancer Inst. 1992 Oct 7;84(19):1512-7. doi: 10.1093/jnci/84.19.1512.
ERCC1 and ERCC2 are human DNA repair genes that are associated with in vitro resistance to selected DNA-damaging agents.
Fresh tumor tissues from 26 patients with ovarian cancer were analyzed for the RNA levels of expression of these genes to determine possible clinical relevance.
Tumor tissues were harvested from patients immediately before they entered a cisplatin- or carboplatin-based treatment protocol. Clinical response was assessed by standard criteria. Gene expression level was assessed by slot blot analysis, using beta-actin as a control. Relative expression levels were determined by comparing each tumor sample with a Chinese hamster ovary cell line that had a stable transfection of the human ERCC1 gene.
Patients who were clinically resistant to platinum-based therapy had a 2.6-fold higher expression level of ERCC1 in their tumor tissue than did patients who responded to that therapy (P = .015). Results obtained by slot blot analysis were qualitatively confirmed by polymerase chain reaction analysis. Relative levels of expression of ERCC2 did not differ significantly between responders and nonresponders.
We conclude that ERCC1 expression levels in human tumor tissue may have a role in clinical resistance to platinum compounds. These data appear to be consistent with the assertion that ERCC1 serves as an excision nuclease, whereas ERCC2 serves as a helicase.
ERCC1和ERCC2是人类DNA修复基因，与对特定DNA损伤剂的体外抗性相关。
分析26例卵巢癌患者新鲜肿瘤组织中这些基因的RNA表达水平，以确定其可能的临床相关性。
在患者进入基于顺铂或卡铂的治疗方案前即刻采集肿瘤组织。通过标准标准评估临床反应。以β-肌动蛋白为对照，通过狭缝印迹分析评估基因表达水平。通过将每个肿瘤样本与稳定转染人ERCC1基因的中国仓鼠卵巢细胞系进行比较来确定相对表达水平。
对铂类疗法临床耐药的患者肿瘤组织中ERCC1的表达水平比有反应的患者高2.6倍（P = 0.015）。狭缝印迹分析获得的结果经聚合酶链反应分析定性证实。ERCC2的相对表达水平在有反应者和无反应者之间无显著差异。
我们得出结论，人类肿瘤组织中ERCC1的表达水平可能在对铂类化合物的临床耐药中起作用。这些数据似乎与ERCC1作为切除核酸酶而ERCC2作为解旋酶的论断一致。
