Introduction: S2R (sigma-2 receptor)/Pgrmc1 (progesterone receptor membrane component 1) is a cytochrome-related protein that binds directly to heme and various pharmacological compounds. S2R Pgrmc1 also associates with cytochrome P450 proteins, the EGFR receptor tyrosine kinase and the RNA-binding protein PAIR-BP1. S2R Pgrmc1 is induced in multiple types of cancer, where it regulates tumor growth and is implicated in progesterone signaling. S2R Pgrmc1 also increases cholesterol synthesis in non-cancerous cells and may have a role in modulating drug metabolizing P450 proteins. Areas covered: This review covers the independent identification of S2R and Pgrmc1 and their induction in cancers, as well as the role of S2R Pgrmc1 in increasing cholesterol metabolism and P450 activity. This article was formed through a PubMed literature search using, but not limited to, the terms sigma-2 receptor, Pgrmc1, Dap1, cholesterol and aromatase. Expert opinion: Multiple laboratories have shown that S2R Pgrmc1 associates with various P450 proteins and increases cholesterol synthesis via Cyp51. However, the lipogenic role of S2R Pgrmc1 is tissue-specific. Furthermore, the role of S2R Pgrmc1 in regulating P450 proteins other than Cyp51 appears to be highly selective, with modest inhibitory activity for Cyp3A4 in vitro and a complex regulatory pattern for Cyp21. Cyp19/aromatase is a therapeutic target in breast cancer, and S2R Pgrmc1 activated Cyp19 significantly in vitro but modestly in biochemical assays. In summary, S2R Pgrmc1 is a promising therapeutic target for cancer and possibly cholesterol synthesis but research to date has not identified a major role in P450-mediated drug metabolism.
|Number of pages||10|
|Journal||Expert Opinion on Drug Metabolism and Toxicology|
|State||Published - Mar 2012|
Bibliographical noteFunding Information:
The authors were supported by the University of Kentucky, the Kentucky Lung Cancer Research Fund and the Kentucky Science and Education Fund.
- Cytochrome P450
- Sigma-2 receptor
ASJC Scopus subject areas