Tryptophanyl-tRNA Synthetase Sensitizes Hormone Receptor-Positive Breast Cancer to Docetaxel-Based Chemotherapy

이경민; 황은혜; 강성은; 이정현; 이혜빈; 오현정; 김광수; 고지원; 류한석

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자료유형: 학술저널

저자정보: 이경민 (Center for Medical Innovation Biomedical Research Institute Seoul National University Hospital Se) 황은혜 (Department of Pathology Seoul National University Hospital Seoul National University College of) 강성은 (Department of Pathology Seoul National University Hospital Seoul National University College of) 이정현 (Department of Pathology Seoul National University Hospital Seoul National University College of) 이혜빈 (Department of Radiation Oncology Kangbuk Samsung Hospital Sungkyunkwan University School of) 오현정 (Department of Pathology Seoul National University Bundang Hospital 82 Gumi-ro 173 Bundang-gu) 김광수 (Transdisciplinary Department of Medicine & Advanced Technology Seoul National University Hospit) 고지원 (Department of Pathology Seoul National University Hospital Seoul National University College of) 류한석 (Center for Medical Innovation Biomedical Research Institute Seoul National University Hospital Seou)

저널정보: 한국유방암학회 Journal of Breast Cancer Journal of Breast Cancer Vol.23 No.6

발행연도: 2020.1

수록면: 599 - 609 (11page)

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Purpose: A relatively low response to chemotherapy has been reported for hormone receptor (HR)-positive breast cancer. In this study, we investigated the role of tryptophanyl-transfer RNA synthetase (WARS) in the chemotherapeutic response of HR-positive breast cancer. Methods: Pre-chemotherapeutic needle biopsy samples of 45 HR-positive breast cancer patients undergoing the same chemotherapeutic regimen were subjected to immunohistochemistry. To investigate the biological functions of WARS in HR-positive breast cancer, we conducted cell viability assay, flow cytometry analysis, caspase activity assay, Quantitative real-time polymerase chain reaction, and western blotting using WARS gene-modulated HR-positive breast cancer cells (T47D, ZR-75-1, and MCF7). Results: WARS overexpression in HR-positive breast cancer patients showed a significant correlation with favorable chemotherapy response. Downregulation of WARS increased cell viability following docetaxel treatment in tumor cell lines. On the other hand, WARS overexpression sensitized the therapeutic response to docetaxel. Additionally, downregulation of WARS caused a decrease in the number of apoptotic cell populations by docetaxel. Poly (ADP-ribose) polymerase cleavage and caspase 3/7 activity were increased in docetaxel-treated tumor cells with WARS overexpression. Conclusion: Our results suggest that WARS might be a potential predictor for chemotherapy response in patients with HR-positive breast cancer as well as a novel molecular target to improve chemosensitivity.

#Apoptosis #Breast neoplasms #Drug resistance #Neoadjuvant therapy #WARS1 protein #human

참고문헌 (25)

참고문헌 신청

Sparano JA / 2018 / Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer / N Engl J Med 379:111~121

Rouzier R / 2005 / Breast cancer molecular subtypes respond differently to preoperative chemotherapy / Clin Cancer Res 11:5678~5685

von Minckwitz G / 2012 / Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes / J Clin Oncol 30:1796~1804

Jin L / 2019 / Expression profile of tRNA-derived fragments in pancreatic cancer / Oncol Lett 18:3104~3114

Yu M / 2020 / tRNA-derived RNA fragments in cancer : current status and future perspectives / J Hematol Oncol 13:121

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이경민

소속기관 Center for Medical Innovation Biomedical Research Institute Seoul National University Hospital Se