机构：[1]Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.四川大学华西医院[2]Breast Cancer Research Center, Chongqing Cancer Institute, Chongqing 400030, P.R. China.
A large proportion (40-60%) of patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer do not benefit from trastuzumab treatment, potentially due to the lack of complement-dependent cytotoxicity (CDC) activation. In the present study, the effect of complement decay-accelerating factor (CD55) and CD59 glycoprotein precursor (CD59) expression on trastuzumab-induced CDC in HER2-positive breast cancer cell lines was investigated. The CD55 and CD59-overexpressing and HER2-positive cell lines SK-BR-3 and BT474 were selected for subsequent experiments. Blocking CD55 and CD59 function using targeting monoclonal antibodies significantly enhanced the cell lysis of SK-BR-3 and BT474 cells following treatment with trastuzumab. In addition, following treatment with 0.1 U/ml phosphatidylinositol-specific phospholipase C (PI-PLC) for 1 h, CD55 and CD59 surface expression was significantly decreased, and the cell lysis rate was further enhanced. Treatment of SK-BR-3 cells with short hairpin RNA (shRNA) targeting CD55 and CD59 downregulated CD55 and CD59 expression at the mRNA and protein levels, and resulted in significantly enhanced trastuzumab-induced CDC-dependent lysis. The data from the present study suggested that CD55 and CD59 serve roles in blocking trastuzumab-induced CDC, therefore strategies targeting CD55 and CD59 may overcome breast cancer cell resistance to trastuzumab. The results from the present study may provide a basis for developing suitable, personalized treatment strategies to improve the clinical efficacy of trastuzumab for patients with HER2-positive breast cancer.
基金：
the National Natural Science Foundation of China (grant no. 30972940).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|4 区医学
小类|4 区肿瘤学
最新[2023]版：
大类|4 区医学
小类|4 区肿瘤学
第一作者：
第一作者机构：[1]Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
共同第一作者：
通讯作者：
通讯机构：[1]Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.[*1]Laboratory of Molecular Diagnosis of Cancer, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041, P.R. China
推荐引用方式(GB/T 7714)：
Wang Yu,Yang Ya-Jun,Wang Zhu,et al.CD55 and CD59 expression protects HER2-overexpressing breast cancer cells from trastuzumab-induced complement-dependent cytotoxicity.[J].Oncology letters.2017,14(3):2961-2969.doi:10.3892/ol.2017.6555.
APA：
Wang Yu,Yang Ya-Jun,Wang Zhu,Liao Juan,Liu Mei...&Wang Yan-Ping.(2017).CD55 and CD59 expression protects HER2-overexpressing breast cancer cells from trastuzumab-induced complement-dependent cytotoxicity..Oncology letters,14,(3)
MLA：
Wang Yu,et al."CD55 and CD59 expression protects HER2-overexpressing breast cancer cells from trastuzumab-induced complement-dependent cytotoxicity.".Oncology letters 14..3(2017):2961-2969
