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RAD51 Mediates Resistance of Cancer Stem Cells to PARP Inhibition in Triple-Negative Breast Cancer 期刊论文

编号：

58362c13-4ab1-4eb9-a1da-7d9b664a70fa
作者：

Liu, Yajing^[1] Burness, Monika L.^[1] MartinTrevino, Rachel^[1] Guy, Joey^[1] Bai, Shoumin^[2] Harouaka, Ramdane^[1] Brooks, Michael D.^[1] Shang, Li^[1] Fox, Alex^[1] Luther, Tahra K.^[1] Davis, April^[1] Baker, Trenton L.^[1] Colacino, Justin^[1] Clouthier, Shawn G.^[1] Shao, Zhiming^[3,4] Wicha, Max S.^[1] Liu, Suling^[5,6]
语种：

English
期刊：

CLINICAL CANCER RESEARCH ISSN：1078-0432 2017 年 23 卷 2 期 (514 - 522) ; JAN
收录：
摘要：

Introduction: PARP inhibitors have shown promising results in early studies for treatment of breast cancer susceptibility gene (BRCA)-deficient breast cancers; however, resistance ultimately develops. Furthermore, the benefit of PARP inhibitors (PARPi) in triple-negative breast cancers (TNBC) remains unknown. Recent evidence indicates that in TNBCs, cells that display "cancer stem cell" properties are resistant to conventional treatments, mediate tumor metastasis, and contribute to recurrence. The sensitivity of breast cancer stem cells (CSC) to PARPi is unknown. Experimental Design: We determined the sensitivity of breast CSCs to PARP inhibition in BRCA1-mutant and -wild-type TNBC cell lines and tumor xenografts. We also investigated the role of RAD51 in mediating CSC resistance to PARPi in these in vitro and in vivo models. Results: We demonstrated that the CSCs in BRCA1-mutant TNBCs were resistant to PARP inhibition, and that these cells had both elevated RAD51 protein levels and activity. Downregulation of RAD51 by shRNA sensitized CSCs to PARP inhibition and reduced tumor growth. BRCA1-wild-type cells were relatively resistant to PARP inhibition alone, but reduction of RAD51 sensitized both CSC and bulk cells in these tumors to PARPi treatment. Conclusions: Our data suggest that in both BRCA1-mutant and BRCA1-wild-type TNBCs, CSCs are relatively resistant to PARP inhibition. This resistance is mediated by RAD51, suggesting that strategies aimed at targeting RAD51 may increase the therapeutic efficacy of PARPi. (C) 2016 AACR.
推荐引用方式
GB/T 7714：

Liu Yajing,Burness Monika L.,Martin-Trevino Rachel, et al. RAD51 Mediates Resistance of Cancer Stem Cells to PARP Inhibition in Triple-Negative Breast Cancer [J].CLINICAL CANCER RESEARCH,2017,23(2):514-522.
APA：

Liu Yajing,Burness Monika L.,Martin-Trevino Rachel,Guy Joey,&Liu Suling.(2017).RAD51 Mediates Resistance of Cancer Stem Cells to PARP Inhibition in Triple-Negative Breast Cancer .CLINICAL CANCER RESEARCH,23(2):514-522.
MLA：

Liu Yajing, et al. "RAD51 Mediates Resistance of Cancer Stem Cells to PARP Inhibition in Triple-Negative Breast Cancer" .CLINICAL CANCER RESEARCH 23,2(2017):514-522.

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