Sigma receptor 1 (SigR1) is an endoplasmic reticulum resident
integral membrane protein whose functions remain unclear. Although the liver shows the highest expression of SigR1, its role in this organ is unknown. SigR1 is overexpressed in many
cancers and its expression is correlated to hormonal status in
hormone-dependent
cancers. To better understand the role of SigR1 in hepatocytes we focused our work on the regulation of its expression in tumoral liver. In this context,
hepatocellular adenomas, benign hepatic
tumors associated with
estrogen intake are of particular interest. The expression of SigR1
mRNA was assessed in
hepatocellular adenoma (HCA) patients using qPCR. The impact of
estrogen on the expression of SigR1 was studied in vivo (mice) and in vitro (HepG2 and Huh7 cells). The effect of HNF1α on the expression of SigR1 was studied in vivo by comparing wild type mice to HNF1 knockout mice.
Estrogen enhanced SigR1 expression through its
nuclear receptor ERα. HNF1α mutated HCA (H-HCA) significantly overexpressed SigR1 compared to all other HCA subtypes. HNF1 knockout mice showed an increase in SigR1 expression. Overexpressing SigR1 in cellular models increases proliferation rate and storage of lipid droplets, which phenocopies the H-HCA phenotype. SigR1 is involved in hepatocyte proliferation and steatosis and may play an important role in the control of the H-HCA phenotype.