Mifepristone Treatment Promotes Testicular Leydig Cell Tumor Progression in Transgenic Mice
Department of Biology and Pathology of Human Reproduction, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland
Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology University of Turku, 20520 Turku, Finland
Department of Medical Pathomorphology, Medical University of Bialystok, 15-269 Bialystok, Poland
College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China
State Key Laboratory of the Agro-Biotechnology, College of Horticultural Science, China Agricultural University, Beijing 100193, China
Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, 15-276 Bialystok, Poland
Department of Pediatrics, Turku University Hospital, 20520 Turku, Finland
Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, UK
Author to whom correspondence should be addressed.
Received: 9 September 2020 / Revised: 27 October 2020 / Accepted: 2 November 2020 / Published: 4 November 2020
Recently, the antiprogestin activity of selective progesterone receptor (PR) modulator mifepristone (MF) has proven unsuccessful as a potential anti-cancer agent in various clinical trials. Herein, we analyzed the effects of MF treatment on Leydig cell tumor (LCT) progression in a transgenic mouse model (inhibin-α promoter-driven SV40 T-antigen), as well as on the proliferation of two Leydig tumor cell lines. MF significantly stimulated the proliferation of LCT in vitro. Similarly, a 1-mo MF or P4 treatment stimulated LCT tumor growth in vivo. Only the abundant membrane Pgrmc1 expression was found in LCTs, but no other classical Pgr or nonclassical membrane PRs. Functional analysis showed that PGRMC1 is required for MF and P4 to stimulate the proliferation and invasiveness of LCTs. Our findings provide novel information that the use of MF as an anti-cancer agent should be considered with caution due to its potential PGRMC1 tumor-promoting pathway activation in cancers.