Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 43, Issue 6, Pages 2212-2225Publisher
KARGER
DOI: 10.1159/000484300
Keywords
Androgen receptor-positive; Estrogen receptor-negative; Breast cancer; Prognosis; Bicalutamide; Antagonize
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Funding
- National Natural Science Foundation of China [81302286]
- China Postdoctoral Science Foundatiion [2016M590209]
- Heilongjiang Natural Science Foundation of China [H2015050]
- Heilongjiang Province scientific research project Fund [201704, 201504]
- State Administration Foreign Experts Affairs China [P172011026]
- Research Fund of The Second Affiliated Hospital of Harbin Medical University [KYBS2015-30]
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Background/Aims: Little is known about the potential mechanism of action for androgen receptor (AR) targeting treatment in estrogen receptor (ER)-negative breast cancer. This study aimed to evaluate AR status and its prognosis in four breast cancer subtypes. Bicalutamide has been identified as an AR antagonist and used for treating AR+/ER- breast cancer in a phase II trial. Our studies will clarify its mechanism in breast cancer treatment. Methods: A total of 510 consecutive cases of invasive ductal cancer (IDC) were evaluated in this study. The expression of AR was analyzed by immunohistochemistry and compared with patient survival, and its implications were evaluated in four subtypes of IDC. We examined bicalutamide as an AR antagonist to inhibit proliferation and increased apoptosis in AR+/ER- breast cancer cell lines. We explored the tumor suppressive functions of bicalutamide in vitro and vivo and its related mechanisms in AR+/ER- breast cancer. Results: AR expression was related to that of ER (P<0.001), PR (P<0.001), Her2 (P=0.017), Ki-67(P=0.020) and to four subtypes (P<0.001). AR retained independent prognostic significance (P=0.007, ER- cases; P=0.001, ER+ cases; P=0.001, total cases). We found that bicalutamide significantly decreased viability and increased apoptosis in vitro and vivo. The mechanistic analysis revealed that bicalutamide blocked androgen-stimulated oncogenic AR and Wnt/beta-catenin signaling and inhibited the growth of AR+/ER- breast cancer. Conclusion: Our studies provide novel insights into bicalutamide as an antagonist of AR function in AR+/ER- breast cancer and reveal the mechanistic basis for targeting AR as a therapeutic opportunity for patients with AR+/ER- breast cancer. (C) 2017 The Author(s) Published by S. Karger AG, Basel
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