Yamaguchi Takahiro, Kurita Tomoko, Nishio Kazuto, Tsukada Junichi, Hachisuga Toru, Morimoto Yasuo, Iwai Yoshiko, Izumi Hiroto
Hematology, University of Occupational and Environmental Health, Kitakyushu, Japan.
Cancer Sci. 2015 Apr;106(4):359-66. doi: 10.1111/cas.12612. Epub 2015 Feb 25.
The SMARCE1 (SWI / SNF-related, matrix-associated, and actin-dependent regulator of chromatin, subfamily e, member 1) encodes BAF57 protein. Previously, we reported that BAF57 is a predictive marker of endometrial carcinoma. In this study, we investigated BAF57 expression in ovarian cancer cell lines and their sensitivities to cisplatin, doxorubicin, paclitaxel, and 5-fluorouracil. BAF57 expression was strongly correlated with sensitivities to cisplatin, doxorubicin, and 5-fluorouracil in 10 ovarian cancer cell lines. Paclitaxel sensitivity was also correlated with BAF57 expression, but without significance. In A2780 ovarian cancer cells, knockdown of BAF57 using specific siRNA increased cell cycle arrest at G1 phase and the sensitivities to these anticancer agents. cDNA microarray analysis of A2780 cells transfected with BAF57 siRNA showed that 134 genes were positively regulated by BAF57, including ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2) encoding breast cancer resistance protein (BCRP). We confirmed that knockdown of BAF57 decreased BCRP expression in ovarian cancer cells by Western blot analysis, and that ABCG2 gene expression might be regulated transcriptionally. These results suggested that BAF57 is involved in ovarian cancer cell growth and sensitivity to anticancer agents, and that BAF57 may be a target for ovarian cancer therapy.
SMARCE1（SWI/SNF相关、基质相关且依赖肌动蛋白的染色质调节因子，e亚家族，成员1）编码BAF57蛋白。此前，我们报道BAF57是子宫内膜癌的一个预测标志物。在本研究中，我们调查了BAF57在卵巢癌细胞系中的表达及其对顺铂、阿霉素、紫杉醇和5-氟尿嘧啶的敏感性。在10个卵巢癌细胞系中，BAF57表达与对顺铂、阿霉素和5-氟尿嘧啶的敏感性密切相关。紫杉醇敏感性也与BAF57表达相关，但无统计学意义。在A2780卵巢癌细胞中，使用特异性小干扰RNA（siRNA）敲低BAF57可增加细胞在G1期的周期阻滞以及对这些抗癌药物的敏感性。对转染了BAF57 siRNA的A2780细胞进行cDNA微阵列分析显示，134个基因受BAF57正向调控，包括编码乳腺癌耐药蛋白（BCRP）的ATP结合盒G亚家族（白色）成员2（ABCG2）。我们通过蛋白质印迹分析证实，敲低BAF57可降低卵巢癌细胞中BCRP的表达，并且ABCG2基因表达可能受转录调控。这些结果表明，BAF57参与卵巢癌细胞的生长及对抗癌药物的敏感性，并且BAF57可能是卵巢癌治疗的一个靶点。
