The epidermal growth factor receptor mediates radioresistance
The epidermal growth factor receptor mediates radioresistance
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DOI：
10.1016/s0360-3016(03)00511-x
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发表时间：
2003-09-01
影响因子：
7
通讯作者：
Fan, Z
中科院分区：
文献类型：
--
作者：
Liang, K;Ang, KK;Fan, Z
目的：表皮生长因子（EGF）受体在恶性肿瘤中经常过度表达，其水平与细胞对电离辐射的抵抗力增加相关。然而，没有先例研究EGF受体的表达本身是否会赋予癌细胞对辐射的抵抗力。目前的研究是为了解决这个问题。方法和材料：一个全长的人EGF受体表达载体转染入OCA-I小鼠卵巢癌细胞表达各种水平的EGF受体的稳定克隆。结果：获得了表达不同水平EGF受体（OCA-I EGFR）的OCA-I细胞克隆。这些克隆表现出EGF受体水平依赖性增加，抗电离辐射，细胞凋亡和细胞克隆生存测定。与亲本OCA-I和对照载体转染的OCA-I细胞在10%细胞存活水平下的结果相比，EGFR-C5（高水平EGF受体表达）、EGFR-C3（中等水平EGF受体表达）和EGFR-C1（低水平EGF受体表达）的放射抗性增加了1.60倍、1.37倍和1.28倍。用EGF受体单克隆抗体C225处理OCA-I EGF受体转染子，可下调EGF受体的水平，降低EGF受体下游底物（如Akt和MALPK）的磷酸化水平，逆转细胞的辐射抗性。结论：EGF受体的过表达可增强细胞对电离辐射的抗性。因此，EGF受体是潜在放射增敏的有效靶点。(C)2003年爱思唯尔公司
Purpose: The epidermal growth factor (EGF) receptor is frequently overexpressed in malignant tumors, and its level is correlated with increased cellular resistance to ionizing radiation. However, no precedent studies have investigated whether expression of EGF receptor would by itself confer on cancer cells resistance to radiation. The current study is aimed to address this question.Methods and Materials: A full-length human EGF receptor expression vector was transfected into the OCA-I murine ovarian carcinoma cells for stable clones expressing various levels of EGF receptors. Apoptosis and cell clonogenic survival assays were used to evaluate the sensitivity of the resulting cell clones to ionizing radiation.Results: OCA-I cell clones expressing various levels of EGF receptor (OCA-I EGFR) were obtained. These clones showed an EGF receptor level-dependent increase in resistance to ionizing radiation, measured by apoptosis and cell clonogenic survival assays. Compared with the results for parental OCA-I and control vector-transfected OCA-I cells at the 10% cell survival level, the radioresistance was increased by a factor of 1.60 for EGFR-C5 (high level of EGF receptor expression), 1.37 for EGFR-C3 (intermediate level of EGF receptor expression), and 1.28 for EGFR-C1 (low level of EGF receptor expression). Treatment of the OCA-I EGF receptor transfectants with the anti-EGF receptor monoclonal antibody C225 downregulated the levels of EGF receptor, reduced the phosphorylation levels of EGF receptor downstream substrates (such as Akt and MALPK), and reversed the cellular radioresistance.Conclusion: Our results demonstrate that overexpression of the EGF receptor conferred cellular resistance to ionizing radiation. The EGF receptor is thus a valid target for potential radiosensitization. (C) 2003 Elsevier Inc.