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Huiru Xiong, Xiaowei Jin, Chuanwen You
(Department of Oncology, Suqian People’s Hospital, Group of Nanjing Drum Tower Hospital, Suqian People’s Hospital Affiliated to Xuzhou Medical University, Suqian, Jiangsu, China (mainland))
Med Sci Monit 2018; 24:7883-7890
Breast cancer is the most prevalent cancer and the leading cause of cancer death among women. Tamoxifen (TAM) therapy is one of the most widely and successfully used endocrine treatments for estrogen receptor α (ERα)-positive breast cancer. However, resistance to TAM has been a major challenge. In addition, the mechanisms underlying endocrine resistance remain unclear. Here, we report that CD59, a phosphatidylinositol-anchored glycoprotein, is a candidate resistant gene for TAM therapies.
MATERIAL AND METHODS: The breast cancer cell line MCF-7, the MCF-10A cell line, and the TAM-resistant breast cancer cell line TAMR-MCF-7 were cultured. The TAMR-MCF-7 cells were transfected with CD59 siRNA and control siRNA. Then, the CD59 glycoprotein precursor expression was detected by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. Cell counting kit-8 and flow cytometry assay were performed to examine cell proliferation, cell apoptosis, and cell cycle. In addition, the expressions of Bax, Bcl2, cleaved-caspase-8, cleaved-caspase-6, cleaved-caspase-3, and cleaved-PARP were analyzed by western blot analysis in the TAMR-MCF-7 cells treated with CD59 siRNA.
RESULTS: In the present study, we found that the CD59 glycoprotein precursor was aberrantly upregulated in the ERα-negative breast cancer MCF-10A cells but not the MCF-7 cells. Furthermore, the CD59 glycoprotein precursor expression was elevated in the TAM-resistant breast cancer cells. Importantly, RNAi-mediated attenuation of CD59 was sufficient to rescue the resistance to TAM in the TAMR-MCF-7 cells.
CONCLUSIONS: In summary, our results proposed a candidate biomarker for predicting TAM resistance in ERa-positive breast cancer via targeting CD59, therefore it could be a novel therapeutic option.