Park S-J, Armstrong S, Kim C-H, Yu M, Robertson K, Kelley M R, Lee S-H
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Br J Cancer. 2005 Jan 31;92(2):334-41. doi: 10.1038/sj.bjc.6602315.
Germline mutations have been associated with generation of various types of tumour. In this study, we investigated genetic alteration of germline tumours that affect the drug sensitivity of cells. Although all germline tumour cells we tested were hypersensitive to DNA-damaging drugs, no significant alteration was observed in their DNA repair activity or the expression of DNA repair proteins. In contrast, germline tumours expressed very low level of epidermal growth factor receptor (EGFR) compared to drug-resistant ovarian cancer cells. An immunohistochemical analysis indicated that most of the primary germline tumours we tested expressed very low level of EGFR. In accordance with this, overexpression of EGFR in germline tumour cells showed an increase in drug resistance, suggesting that a lack of EGFR, at least in part, contributes to the drug sensitivity of germline tumours.
种系突变与多种类型肿瘤的发生有关。在本研究中，我们调查了影响细胞药物敏感性的种系肿瘤的基因改变。尽管我们测试的所有种系肿瘤细胞对DNA损伤药物均高度敏感，但未观察到它们的DNA修复活性或DNA修复蛋白表达有明显改变。相比之下，与耐药性卵巢癌细胞相比，种系肿瘤中表皮生长因子受体（EGFR）的表达水平非常低。免疫组织化学分析表明，我们测试的大多数原发性种系肿瘤EGFR表达水平非常低。据此，种系肿瘤细胞中EGFR的过表达显示耐药性增加，这表明EGFR的缺乏至少部分导致了种系肿瘤的药物敏感性。
