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  • Title: Essential Role of Polo-like Kinase 1 (Plk1) Oncogene in Tumor Growth and Metastasis of Tamoxifen-Resistant Breast Cancer.
    Author: Jeong SB, Im JH, Yoon JH, Bui QT, Lim SC, Song JM, Shim Y, Yun J, Hong J, Kang KW.
    Journal: Mol Cancer Ther; 2018 Apr; 17(4):825-837. PubMed ID: 29437878.
    Abstract:
    The most common therapy for estrogen receptor-positive breast cancer is antihormone therapy, such as tamoxifen. However, acquisition of resistance to tamoxifen in one third of patients presents a serious clinical problem. Polo-like kinase 1 (Plk1) is a key oncogenic regulator of completion of G2-M phase of the cell cycle. We assessed Plk1 expression in five chemoresistant cancer cell types and found that Plk1 and its downstream phosphatase Cdc25c were selectively overexpressed in tamoxifen-resistant MCF-7 (TAMR-MCF-7) breast cancer cells. Real-time monitoring of cell proliferation also showed that TAMR-MCF-7 cells were more sensitive to inhibition of cell proliferation by the ATP-competitive Plk1 inhibitor BI2536 than were the parent MCF-7 cells. Moreover, BI2536 suppressed expression of epithelial-mesenchymal transition marker proteins and 3D spheroid formation in TAMR-MCF-7 cells. Using TAMR-MCF-7 cell-implanted xenograft and spleen-liver metastasis models, we showed that BI2536 inhibited tumor growth and metastasis in vivo Our results suggest that Plk1 could be a novel target for the treatment of tamoxifen-resistant breast cancer. Mol Cancer Ther; 17(4); 825-37. ©2018 AACR.
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