Differential impact of cytoplasmic vs. nuclear RAD51 expression on breast cancer progression and patient prognosis

Wang,Yen-Yun; Cheng,Kuang-Hung; Hung,Amos C.; Lo,Steven; Chen,Pang-Yu; Wu,Yi-Chia; Hou,Ming-Feng; Yuan,Shyng-Shiou F.

doi:10.3892/ijo.2023.5600

Differential impact of cytoplasmic vs. nuclear RAD51 expression on breast cancer progression and patient prognosis

Authors:
- Yen-Yun Wang
- Kuang-Hung Cheng
- Amos C. Hung
- Steven Lo
- Pang-Yu Chen
- Yi-Chia Wu
- Ming-Feng Hou
- Shyng-Shiou F. Yuan
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Affiliations: School of Dentistry, College of Dental Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, R.O.C., Institute of Biomedical Sciences, National Sun Yat‑Sen University, Kaohsiung 804, Taiwan, R.O.C., Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK, Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C., Drug Development and Value Creation Research Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, R.O.C.
Published online on: December 7, 2023 https://doi.org/10.3892/ijo.2023.5600
Article Number: 12
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

RAD51 recombinase is one of the DNA damage repair proteins associated with breast cancer risk. Apart from its function to maintain genomic integrity within the cell nucleus, RAD51 localized to the cytoplasm has also been implicated in breast malignancy. However, limited information exists on the roles of cytoplasmic vs. nuclear RAD51 in breast cancer progression and patient prognosis. In the present study, the association of cytoplasmic and nuclear RAD51 with clinical outcomes of patients with breast cancer was analyzed, revealing that elevated cytoplasmic RAD51 expression was associated with breast cancer progression, including increased cancer stage, grade, tumor size, lymph node metastasis and chemoresistance, along with reduced patient survival. By contrast, elevated nuclear RAD51 expression largely had the inverse effect. Results from in vitro investigations supported the cancer‑promoting effect of RAD51, showing that overexpression of RAD51 promoted breast cancer cell growth, chemoresistance and metastatic ability, while knockdown of RAD51 repressed these malignant behaviors. The current data suggest that differential expression of subcellular RAD51 had a distinct impact on breast cancer progression and patient survival. Specifically, cytoplasmic RAD51 in contrast to nuclear RAD51 was potentially an adverse marker in breast cancer.

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