The Correlation Between PARP1 and BRCA1 in AR Positive Triple-negative Breast Cancer.
The Correlation Between PARP1 and BRCA1 in AR Positive Triple-negative Breast Cancer.
复制标题
AR 阳性三阴性乳腺癌中 PARP1 和 BRCA1 的相关性。
DOI：
10.7150/ijbs.16176
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发表时间：
2016
影响因子：
9.2
通讯作者：
Guan X
中科院分区：
文献类型：
--
作者：
Luo J;Jin J;Yang F;Sun Z;Zhang W;Shi Y;Xu J;Guan X
三阴性乳腺癌（TNBC）缺乏雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER-2）表达，因此无法从传统的激素或抗HER2靶向治疗中受益。抗雄激素治疗对雄激素受体（AR）阳性的TNBC显示出一定的疗效。最新研究证明，聚（ADP-核糖）聚合酶（PARP）抑制剂对 BRCA1 缺陷型乳腺癌有效。我们证明，无论在体外还是体内环境下，AR 阳性 TNBC 中 AR 拮抗剂（比卡鲁胺）和 PARP 抑制剂（ABT-888）的组合都可以显着抑制细胞活力并诱导细胞凋亡。既往研究已证明BRCA1和PARP1均与前列腺癌中的AR有密切关系。我们首次探讨了 TNBC 中 AR、PARP1 和 BRCA1 之间的相关性。 BRCA1过表达后，AR和PARP1的mRNA和蛋白水平表达降低。此外，AR 正向调节 PARP1，而 PARP1 也在体外上调 AR 表达。我们还使用 TNBC 患者样本的组织微阵列证实了 TNBC 患者中 BRCA1 表达与 AR 和 PARP1 呈负相关。这些结果表明，比卡鲁胺和 PARP 抑制剂的联合治疗可能是 TNBC 患者的潜在策略，值得进一步评估。
Triple-negative breast cancer (TNBC) lacks estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression and thus cannot benefit from conventional hormonal or anti-HER2 targeted therapies. Anti-androgen therapy has shown a certain effect on androgen receptor (AR) positive TNBC. The emerging researches have proved that poly (ADP-ribose) polymerase (PARP) inhibitor is effective in BRCA1-deficient breast cancers. We demonstrated that combination of AR antagonist (bicalutamide) and PARP inhibitor (ABT-888) could inhibit cell viability and induce cell apoptosis significantly whatever in vitro or in vivo setting in AR-positive TNBC. Previous studies have proved that both BRCA1 and PARP1 have close connections with AR in prostate cancer. We explored the correlation among AR, PARP1 and BRCA1 in TNBC for the first time. After BRCA1 overexpression, the expression of AR and PARP1 were decreased in mRNA and protein levels. Additionally, AR positively regulated PARP1 while PARP1 also up-regulated AR expression in vitro. We also confirmed BRCA1 expression was negatively correlated with AR and PARP1 in TNBC patients using a tissue microarray with TNBC patient samples. These results suggest that the combination of bicalutamide and PARP inhibitor may be a potential strategy for TNBC patients and merits further evaluation.
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影响因子：
4.3
作者：
Helleday, T;Bryant, HE;Schultz, N
通讯作者：
Schultz, N
影响因子：
9
作者：
Li, H.;Li, Y.;Morin, D.;Plymate, S.;Lye, S.;Dong, X.
通讯作者：
Dong, X.
影响因子：
5.8
作者：
Liu, Liangliang;Li, Yunqing;Dong, Xuesen
通讯作者：
Dong, Xuesen
DOI：
10.1158/1078-0432.ccr-10-0939
发表时间：
2010-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Anders CK;Winer EP;Ford JM;Dent R;Silver DP;Sledge GW;Carey LA
通讯作者：
Carey LA
影响因子：
50.3
作者：
Ni M;Chen Y;Lim E;Wimberly H;Bailey ST;Imai Y;Rimm DL;Liu XS;Brown M
通讯作者：
Brown M