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 alpha (mPR alpha) is expressed in TNBC tissues and the expression level of mPR alpha is negatively associated with the TNM stage. We found that progesterone suppressed the growth, migration and invasion of mPR alpha(+) 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 mPR alpha. Moreover, the knockdown of mPR alpha expression impaired the inhibitory effects of progesterone on mPR alpha(+) tumor growth and metastasis in vivo. These data collectively indicate that progesterone suppresses TNCB growth and metastasis via mPR alpha, which provides evidence of the anti-neoplastic effects of progesterone-mPR alpha pathway in the treatment of human TNBC.
[1]Shanghai Pudong New Dist Zhoupu Hosp, Dept Oncol & Hematol, Shanghai 201318, Peoples R China.
[2]Shanghai Seventh Peoples Hosp, Dept Oncol, Shanghai 200137, Peoples R China.
[3]Shanghai Seventh Peoples Hosp, Dept Intervent, Shanghai 200137, Peoples R China.
[4]Shanghai Seventh Peoples Hosp, Dept Nucl Med, 358 Datong Rd, Shanghai 200137, Peoples R China.
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