Progesterone receptor membrane component-1 promotes cancer cell proliferation and resistance to anthracycline treatment in breast cancer
09 May 2017 (online)
Progesterone receptor membrane component 1 (PGRMC1) is upregulated in breast cancer tumors and is reported to be associated with progesterone-induced cell survival. However, PGRMC1 signaling and its role in breast cancer progression and therapy resistance is not fully understood yet.
Therefore, this study was designed to investigate the involvement of PGRMC1 in regulating proliferation and survival of breast cancer cells. Tissue biopsies of 69 breast cancer patients were analyzed by immunohistochemistry for expression levels of PGRMC1 and pPGRMC1. Correlations were calculated for expression of PGRMC1 and pPGRMC1 before and after neoadjuvant-therapy. Various breast cancer celllines were stably transfected with plasmids expressing HA-tagged PGRMC1 wildtype protein and impact of PGRMC1 over-expression on cell proliferation and treatment with anthracyclines was investigated by MTT assay. PGRMC1 and pPGRMC1 were highly abundant in every breast cancer tissue sample. A lower level of pPGRMC1 could be found in post-therapy tumor tissue compared to tumors before treatment. Interestingly, anthracycline-treated patients who showed stable disease, revealed a higher PGRMC1 expression in tumor tissue as compared to patients with partial remission. In in vitro studies, over-expression of PGRMC1 resulted in increased proliferation of breast cancer cells compared to the empty vector control cell lines. Moreover, cells overexpressing PGRMC1 showed decreased susceptibility to the chemotherapeutic agents Doxorubicin and Epirubicin when pre-treated with the PGRMC1 ligand Progesterone. These new findings demonstrate that PGRMC1 might play an important role in progression and therapy resistance of human breast tumors and could offer an interesting target for anti-cancer therapy.