Elements in support of the 'non-identity' of the PGRMC1 protein with the σ₂ receptor

σ₂ Receptor subtype is overexpressed in a variety of human tumors, with σ₂ agonists showing antiproliferative effects towards tumor cells through multiple pathways that depend both on the tumor cell type and on the molecule type. Therefore, σ₂ receptor is an intriguing target for tumor diagnosis and treatment despite the fact that that it has not yet been cloned. One of the last attempts to characterize σ₂ receptors led to identify it as the progesterone receptor membrane component 1 (PGRMC1). Although still controversial, such identity appears to have been accepted. We the aim of contributing to solve this controversy, in this work we stably silenced or overexpressed PGRMC1 protein in human MCF7 adenocarcinoma cells. Western blotting analyses were performed to quantify the presence of PGRMC1 protein on each of the three MCF7 cell lines variants, while scatchard analyses with radioligand were performed in order to determine the expression of the σ₂ receptors. In order to correlate the antiproliferative effect of σ₂ receptor agonist with PGRMC1 density, some σ₂ ligands were administered to each of the three MCF7 cells variants. The results suggested that PGRMC1 and σ₂ receptors are two different molecular entities.