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.
Int J Oncol. 2024 Feb;64(2). doi: 10.3892/ijo.2023.5600. Epub 2023 Dec 8.
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 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.
RAD51 重组酶是与乳腺癌风险相关的 DNA 损伤修复蛋白之一。除了在细胞核内维持基因组完整性的功能外,定位于细胞质的 RAD51 也与乳腺癌恶性肿瘤有关。然而,关于细胞质与核 RAD51 在乳腺癌进展和患者预后中的作用的信息有限。在本研究中,分析了细胞质和核 RAD51 与乳腺癌患者临床结局的关系,结果表明细胞质 RAD51 表达升高与乳腺癌进展相关,包括癌症分期、分级、肿瘤大小、淋巴结转移和化疗耐药性增加,以及患者生存率降低。相比之下,核 RAD51 表达升高则具有相反的作用。来自研究的结果支持 RAD51 的致癌作用,表明 RAD51 的过表达促进了乳腺癌细胞的生长、化疗耐药性和转移能力,而 RAD51 的敲低则抑制了这些恶性行为。目前的数据表明,亚细胞 RAD51 的差异表达对乳腺癌的进展和患者的生存有明显的影响。具体来说,细胞质 RAD51 与核 RAD51 相反,可能是乳腺癌的不良标志物。