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Involvement of Polo‐like kinase 1 (Plk1) in tumor growth and epithelial‐mesenchymal transition of tamoxifen‐resistant breast cancer
Author(s) -
Jeong Sung Baek,
Kang Keon Wook
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb536
Subject(s) - tamoxifen , cancer research , metastasis , breast cancer , epithelial–mesenchymal transition , cell growth , plk1 , cancer , cell cycle , kinase , medicine , biology , microbiology and biotechnology , genetics
The most common therapy for estrogen receptor‐positive breast cancer is anti‐hormone therapy such as tamoxifen treatment. However, one‐third of the patients acquires tamoxifen resistance and become a serious clinical problem. Polo‐like kinase 1 (Plk1) is a key regulator for the completion of G2/M phase cell cycle. When we assessed Plk1 expression in six chemo‐resistant cancer cell sets, we 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 BI2536 (ATP‐competitive Plk1 inhibitor)‐mediated inhibition of cell proliferation was more sensitive in TAMR‐MCF‐7 cells than the parent MCF‐7 cells. Moreover, we observed that BI2536 suppressed the expression of epithelial‐mesenchymal transition (EMT) marker proteins and 3D‐spheroid formation in TAMR‐MCF‐7 cells. By using TAMR‐MCF‐7 cells‐implanted xenograft and spleen‐liver metastasis models, we observed that BI2536 inhibited tumor growth and metastasis in vivo . Our results propose that Plk1 could be a novel target for the treatment of tamoxifen‐resistant breast cancer. Support or Funding Information This work was supported by a grant (2014M3A9A9073788) from National Research Foundation of Korea, Republic of Korea.