PGRMC1 predicts poor prognosis and promotes tumour progression of breast cancer through upregulation of ERα expression

PGRMC1 was reported to be upregulated in breast cancer and elevated expression of PGRMC1 was associated with increased tumour growth and poorer outcome, suggesting a contribution of PGRMC1 on carcinogenesis of breast cancer. However, the mechanism by which PGRMC1 contributes to breast cancer progression is not fully understood yet. Therefore, the aim of the present study was to further investigate how PGRMC1 is involved in breast cancer progression.

For this purpose, the effect of PGRMC1 overexpression and -knockdown on cell proliferation was examined in vivo and in vitro. With the aim to gain deeper insight into PGRMC1 signalling in breast cancer we further searched for potential proteins and signalling pathways which might be regulated by PGRMC1. A special focus was placed on PGRMC1-dependent expression and activity of ERα.

Using TCGA expression data of breast cancer patients, we found correlation of high PGRMC1 expression with poorer overall survival. Overexpression of PGRMC1 in the hormone-receptor positive cell lines MCF7 and T47D resulted in significantly increased proliferation, while knockdown of PGRMC1 caused significantly decreased proliferation. Interestingly for the basal-like cell line MDA-MB-231 cells, we did not observe any effect of altered PGRMC1 expression on cell proliferation. Analysis of PGRMC1-dependent expression and activation of proteins revealed upregulation of ERα and ERα-dependent genes, as well as activation of EGFR signalling cascade.

Our results again demonstrate an important role of PGRMC1 in breast cancer progression and embedding of PGRMC1 in essential breast cancer signalling pathways. PGRMC1 might therefore be an interesting target for anti-cancer therapy.