Association of BRCA Mutantations and BRCAness Status With Anticancer Drug Sensitivities in Triple-Negative Breast Cancer Cell Lines
Association of BRCA Mutantations and BRCAness Status With Anticancer Drug Sensitivities in Triple-Negative Breast Cancer Cell Lines
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三阴性乳腺癌细胞系中 BRCA 突变和 BRCA 状态与抗癌药物敏感性的关联
DOI：
10.1016/j.jss.2019.12.040
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Ishikawa T.
中科院分区：
文献类型：
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作者：
Teraoka S;Muguruma M;Takano N;Miyahara K;Kawate T;Kaise H;Yamada K;Miyazawa K;Ishikawa T.
背景许多三阴性乳腺癌（triple-negative breast cancers，TNBC）患者的乳腺癌易感基因I（breast cancer susceptibility gene I，BRCA 1）功能受损，称为BRCAness。BRCA阴性肿瘤对抗癌药物的敏感性可能与BRCA 1突变肿瘤相似。在这项研究中，我们调查了BRCA突变或BRCAness与药物敏感性在TNBC.MethodsBRCAness评估为BRCA 1样评分，使用多重连接依赖的探针扩增在12 TNBC细胞系，包括4个突变。对多西他赛、顺铂和表阿霉素的敏感性与BRCA突变和BRCA 1样评分进行比较。顺铂敏感性在BRCA 1敲低密歇根州癌症基金会-7细胞line.Results8和4细胞株BRCAness和non-BRCAness的特点，分别进行了检查。多西他赛对BRCAmutant和BRCAness细胞株的50%抑制浓度均高于相应细胞株，BRCA 1样评分与多西他赛敏感性呈弱正相关（r= 0.377;P= 0.039）。关于顺铂，BRCA突变体和BRCAness肿瘤的评分低于其对应物。BRCA 1样评分与顺铂敏感性呈负相关（r=-0.407;P= 0.013）。BRCA 1基因敲低可增加Michigan Cancer Foundation-7细胞对顺铂的敏感性。因此，BRCA 1样评分是估计TNBC药物敏感性的有希望的指标。
BackgroundMany triple-negative breast cancers (TNBCs) show impaired breast cancer susceptibility gene I (BRCA1) function, called BRCAness. BRCAness tumors may show similar sensitivities to anticancer drugs as tumors withBRCA1mutations. In this study, we investigated the association ofBRCAmutations or BRCAness with drug sensitivities in TNBC.MethodsBRCAness was evaluated asBRCA1-like scores, using multiplex ligation-dependent probe amplification in 12 TNBC cell lines, including four with mutations. Sensitivities to docetaxel, cisplatin, and epirubicin were compared withBRCAmutations andBRCA1-like scores. Cisplatin sensitivity was examined inBRCA1knockdown Michigan Cancer Foundation-7 cell lines.ResultsEight and four cell lines had characteristics of BRCAness and non-BRCAness, respectively. The 50% inhibitory concentration of docetaxel was higher inBRCAmutant and BRCAness cell lines than their counterparts.BRCA1-like scores showed a weak positive correlation with docetaxel sensitivity (r= 0.377;P= 0.039). Regarding cisplatin, scores were lower inBRCAmutants and BRCAness tumors than their counterparts. A negative correlation was found betweenBRCA1-like scores and cisplatin sensitivity (r= −0.407;P= 0.013). No differences were found for epirubicin.BRCA1gene knockdown increased the cisplatin sensitivity of Michigan Cancer Foundation-7 cells.ConclusionsBRCA1-like scores were associated with cisplatin sensitivity and docetaxel resistance. BRCA1-like score is hence a promising indicator for estimating drug sensitivities in TNBC.