2. Academic Validation
  3. Essential Role of Polo-like Kinase 1 (Plk1) Oncogene in Tumor Growth and Metastasis of Tamoxifen-Resistant Breast Cancer

Essential Role of Polo-like Kinase 1 (Plk1) Oncogene in Tumor Growth and Metastasis of Tamoxifen-Resistant Breast Cancer

  • Mol Cancer Ther. 2018 Apr;17(4):825-837. doi: 10.1158/1535-7163.MCT-17-0545.
Sung Baek Jeong 1,  Ji Hye Im 1,  Jeong-Hoon Yoon 2,  Quyen Thu Bui 1,  Sung Chul Lim 3,  Joon Myong Song 1,  Yumi Shim 1,  Jieun Yun 4,  Janghee Hong 5,  Keon Wook Kang 6
Affiliations

Affiliations

  • 1 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
  • 2 Department of Oral & Maxillofacial Pathology, College of Dentistry, Daejeon Dental Hospital, Wonkwang University, Daejeon, South Korea.
  • 3 Department of Pathology, College of Medicine, Chosun University, Gwangju, South Korea.
  • 4 Department of Pharmaceutical Engineering, College of Science & Engineering, Cheongju University, Cheongju, South Korea.
  • 5 Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, South Korea.
  • 6 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea. [email protected].
PMID: 29437878 DOI: 10.1158/1535-7163.MCT-17-0545
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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