RNF126 as a biomarker of a poor prognosis in invasive breast cancer and CHK1 inhibitor efficacy in breast cancer cells | |
Shanhuai Ma9; Pengyan Fa9; Zhefu Ma7,8; Hongbing Wang3; Yao Zhang9; Zhanwen Du9; Zhaojun Qiu9; Junran Zhang9; Shashank Gorityala1; Ceshi Chen2 | |
刊名 | Clinical Cancer Research |
2018 | |
卷号 | 24期号:7页码:1629-1643 |
关键词 | Rnf126 Chk1 Replication Stress Breast Cancer Target Therapy |
DOI | 10.1158/1078-0432.CCR-17-2242 |
英文摘要 | Purpose: 1) To investigate expression of the E3 ligase, RNF126, in human invasive breast cancer (BC)and its links with BC outcomes. 2) To test the hypothesis that RNF126 determines the efficacy ofinhibitors targeting the cell cycle checkpoint kinase, CHK1. Experimental Design: A retrospective analysis by immunohistochemistry (IHC) compared RNF126staining in 110 invasive BC and 78 paired adjacent normal tissues with clinicopathologic data. WhetherRNF126 controls CHK1 expression was determined by chromatin immunoprecipitation and a CHK1promoter driven luciferase reporter. Staining for these two proteins by IHC using tissue microarrays wasalso conducted. Cell killing/replication stress induced by CHK1 inhibition was evaluated in cells, with orwithout RNF126 knockdown, by MTT/colony formation, replication stress biomarker immunostainingand DNA fiber assays. Results: RNF126 protein expression was elevated in BC tissue samples. RNF126 was associated witha poor clinical outcome after multivariate analysis and was an independent predictor. RNF126promotes CHK1 transcript expression. Critically, a strong correlation between RNF126 and CHK1proteins was identified in BC tissue and cell lines. The inhibition of CHK1 induced a greater cell killingand a higher level of replication stress in BC cells expressing RNF126 compared to RNF126 depletedcells. Conclusions: RNF126 protein is highly expressed in invasive BC tissue. The high expression ofRNF126 is an independent predictor of a poor prognosis in invasive BC and is considered a potentialbiomarker of a cancer’s responsiveness to CHK1 inhibitors. CHK1 inhibition targets BC cells expressinghigher levels of RNF126 by enhancing replication stress. |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://159.226.149.26:8080/handle/152453/12373] |
专题 | 昆明动物研究所_肿瘤生物学 |
通讯作者 | Zhefu Ma |
作者单位 | 1.Department of Chemistry, Cleveland State University, Cleveland. 2.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China. 3.Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland. 4.Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio. 5.Georgia Cancer Center, Augusta University, Georgia 6.Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio. 7.Department of Breast Surgery & Plastic Surgery, Cancer Hospital of China Medical University, Shenyang, China. 8.Department of Breast Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 9.Department of Radiation Oncology, School of Medicine, Case Western Reserve University, Cleveland, Ohio. 10.Division of Oncology Breast Oncology Section, Washington University Medical School, St. Louis, Missouri. |
推荐引用方式 GB/T 7714 | Shanhuai Ma,Pengyan Fa,Zhefu Ma,et al. RNF126 as a biomarker of a poor prognosis in invasive breast cancer and CHK1 inhibitor efficacy in breast cancer cells[J]. Clinical Cancer Research,2018,24(7):1629-1643. |
APA | Shanhuai Ma.,Pengyan Fa.,Zhefu Ma.,Hongbing Wang.,Yao Zhang.,...&Keri Ruth.(2018).RNF126 as a biomarker of a poor prognosis in invasive breast cancer and CHK1 inhibitor efficacy in breast cancer cells.Clinical Cancer Research,24(7),1629-1643. |
MLA | Shanhuai Ma,et al."RNF126 as a biomarker of a poor prognosis in invasive breast cancer and CHK1 inhibitor efficacy in breast cancer cells".Clinical Cancer Research 24.7(2018):1629-1643. |
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