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Cancer Biology and Translational Studies

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

Sung Baek Jeong, Ji Hye Im, Jeong-Hoon Yoon, Quyen Thu Bui, Sung Chul Lim, Joon Myong Song, Yumi Shim, Jieun Yun, Janghee Hong and Keon Wook Kang
Sung Baek Jeong
1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
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Ji Hye Im
1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
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Jeong-Hoon Yoon
2Department of Oral & Maxillofacial Pathology, College of Dentistry, Daejeon Dental Hospital, Wonkwang University, Daejeon, South Korea.
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Quyen Thu Bui
1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
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Sung Chul Lim
3Department of Pathology, College of Medicine, Chosun University, Gwangju, South Korea.
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Joon Myong Song
1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
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Yumi Shim
1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
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Jieun Yun
4Department of Pharmaceutical Engineering, College of Science & Engineering, Cheongju University, Cheongju, South Korea.
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Janghee Hong
5Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, South Korea.
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Keon Wook Kang
1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
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  • For correspondence: kwkang@snu.ac.kr
DOI: 10.1158/1535-7163.MCT-17-0545 Published April 2018
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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.

  • Received June 14, 2017.
  • Revision received October 17, 2017.
  • Accepted February 1, 2018.
  • Published first February 7, 2018.
  • ©2018 American Association for Cancer Research.
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Molecular Cancer Therapeutics: 17 (4)
April 2018
Volume 17, Issue 4
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Essential Role of Polo-like Kinase 1 (Plk1) Oncogene in Tumor Growth and Metastasis of Tamoxifen-Resistant Breast Cancer
Sung Baek Jeong, Ji Hye Im, Jeong-Hoon Yoon, Quyen Thu Bui, Sung Chul Lim, Joon Myong Song, Yumi Shim, Jieun Yun, Janghee Hong and Keon Wook Kang
Mol Cancer Ther April 1 2018 (17) (4) 825-837; DOI: 10.1158/1535-7163.MCT-17-0545

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Essential Role of Polo-like Kinase 1 (Plk1) Oncogene in Tumor Growth and Metastasis of Tamoxifen-Resistant Breast Cancer
Sung Baek Jeong, Ji Hye Im, Jeong-Hoon Yoon, Quyen Thu Bui, Sung Chul Lim, Joon Myong Song, Yumi Shim, Jieun Yun, Janghee Hong and Keon Wook Kang
Mol Cancer Ther April 1 2018 (17) (4) 825-837; DOI: 10.1158/1535-7163.MCT-17-0545
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