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Essential role of Polo-like kinase 1 (Plk1) oncogene in tumor growth and metastasis of tamoxifen-resistant breast cancer
Cited 45 time in
Web of Science
Cited 48 time in Scopus
- Authors
- Issue Date
- 2018-04
- Publisher
- American Association for Cancer Research
- Citation
- Molecular Cancer Therapeutics, Vol.17 No.4, pp.825-837
- 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 G(2)-M phase of the cell cycle. We assessed Plk1 expression in five chemoresistant cancer cell types and found that Plk1 and its downstreamphosphatase 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.
- ISSN
- 1535-7163
- Language
- English
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