Progesterone suppresses triple-negative breast cancer growth and metastasis to the brain via membrane progesterone receptor α

Zhou,Li; Zhou,Wei; Zhang,Hongwei; Hu,Yan; Yu,Lei; Zhang,Yufei; Zhang,Yanli; Wang,Shuang; Wang,Peng; Xia,Wei

doi:10.3892/ijmm.2017.3060

Progesterone suppresses triple-negative breast cancer growth and metastasis to the brain via membrane progesterone receptor α

Authors:
- Li Zhou
- Wei Zhou
- Hongwei Zhang
- Yan Hu
- Lei Yu
- Yufei Zhang
- Yanli Zhang
- Shuang Wang
- Peng Wang
- Wei Xia
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Affiliations: Department of Oncology and Hematology, Shanghai Pudong New District Zhoupu Hospital, Shanghai 201318, P.R. China, Department of Oncology, Shanghai Seventh People's Hospital, Shanghai 200137, P.R. China, Department of Intervention, Shanghai Seventh People's Hospital, Shanghai 200137, P.R. China, Department of Nuclear Medicine, Shanghai Seventh People's Hospital, Shanghai 200137, P.R. China
Published online on: July 7, 2017 https://doi.org/10.3892/ijmm.2017.3060
Pages: 755-761
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Progesterone plays an important role in mammary epithelial cell proliferation and differentiation. Evidence from experimental and clinical studies indicates that progesterone is a risk factor for breast cancer under certain conditions through binding nuclear progesterone receptor (PR). These mechanisms, however, are not applicable to triple-negative breast cancer (TNBC) due to the lack of PR in these cancers. In this study, we demonstrate that membrane progesterone receptor α (mPRα) is expressed in TNBC tissues and the expression level of mPRα is negatively associated with the TNM stage. We found that progesterone suppressed the growth, migration and invasion of mPRα+ human TNBC cells in vitro, which was neither mediated by PR nor by PR membrane component 1 (PGRMCl). Notably, these effects exerted by progesterone were significantly blocked by shRNA specific to mPRα. Moreover, the knockdown of mPRα expression impaired the inhibitory effects of progesterone on mPRα+ tumor growth and metastasis in vivo. These data collectively indicate that progesterone suppresses TNCB growth and metastasis via mPRα, which provides evidence of the anti-neoplastic effects of progesterone-mPRα pathway in the treatment of human TNBC.

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