单位：[1]Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China[2]Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA[3]Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA[4]Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, Jilin, 130033, China吉林大学中日联谊医院[5]Department of Pathology, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA[6]Department of Surgery, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA[7]Department of Pathology, China-Japan Friendship Hospital, Beijing, China[8]College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, China
Intrinsic or acquired chemoresistance is a hurdle in oncology. Only 7%-16% of estrogen receptor a (ERa) positive breast cancer cases achieve a pathological complete response (pCR) after neo-adjuvant chemotherapy. Nogo-B receptor (NgBR) is a cell surface receptor that binds farnesylated Ras and promotes Ras translocation to the plasma membrane. Here, we demonstrate NgBR as a potential therapeutic target for ERa positive breast cancer patients to attenuate paclitaxel resistance. NgBR knockdown enhanced paclitaxel-induced cell apoptosis by modulating expression of p53 and survivin in ERa positive breast cancer cells via NgBR-mediated PI3K/Akt and MAPK/ERK signaling pathways. NgBR knockdown attenuated either 1713-estradiol or epidermal growth factor stimulated phosphorylation of ERa at Serine 118 residue. The ChIP-PCR assay further demonstrated that NgBR knockdown decreased ERa binding to the estrogen response element (ERE) of the ERa target gene and increased the binding of p53 to the promoter region of survivin to attenuate survivin transcription. In summary, our data suggest that NgBR expression is essential to promoting ERa positive breast cancer cell resistance to paclitaxel. Findings from this study implicate a novel therapeutic target for treating ERa positive breast cancer in neo-adjuvant/adjuvant chemotherapy. (C) 2018 Elsevier B.V. All rights reserved.
基金：
Division of Pediatric Surgery, Medical College of Wisconsin (MCW); Division of Pediatric Pathology, Medical College of Wisconsin (MCW); Advancing a Healthier Wisconsin endowment; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01HL108938]; Wisconsin Breast Cancer Showhouse (WBCS); American Cancer SocietyAmerican Cancer Society [86-004-26]; Kathy Duffey Fogarty Award for breast cancer research; State of Wisconsin Tax Check-off program for breast & prostate cancer research; We Care Fund; Children's Hospital of Wisconsin Research Institute Pilot Innovative Research Grant; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81041098]; Bethune Program B of Jilin University [2012217]; NATIONAL HEART, LUNG, AND BLOOD INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL108938] Funding Source: NIH RePORTER
第一作者单位：[1]Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China[2]Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA[3]Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA
通讯作者：
通讯机构：[1]Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China[2]Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA[3]Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, 8701 W Watertown Plank Rd, Milwaukee, WI, 53226, USA[*1]Division of Pediatric Surgery and Division of Pediatric Pathology, Department of Surgery and Department of Pathology, Medical College of Wisconsin, Children's Research Institute, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA[*2]Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, China
推荐引用方式(GB/T 7714)：
Jin Ying,Hu Wenquan,Liu Tong,et al.Nogo-B receptor increases the resistance of estrogen receptor positive breast cancer to paclitaxel[J].CANCER LETTERS.2018,419:233-244.doi:10.1016/j.canlet.2018.01.054.
APA：
Jin, Ying,Hu, Wenquan,Liu, Tong,Rana, Ujala,Aguilera-Barrantes, Irene...&Miao, Qing Robert.(2018).Nogo-B receptor increases the resistance of estrogen receptor positive breast cancer to paclitaxel.CANCER LETTERS,419,
MLA：
Jin, Ying,et al."Nogo-B receptor increases the resistance of estrogen receptor positive breast cancer to paclitaxel".CANCER LETTERS 419.(2018):233-244
医学