The expression and functional characterization of sigma (σ) 1 receptors in breast cancer cell lines

Sigma (a) receptors have been implicated in cancer. However, to date there is little molecular data demonstrating the role of sigma 1 receptors in cancer. Expression of sigma 1 receptors in various human cancer cell lines in comparison to non-cancerous cell lines was investigated, using real time RT-PCR and by western blotting with a sigma 1 receptor specific antibody. Our results indicate that cancer cells express higher levels of sigma 1 receptors than corresponding non-cancerous cells. Localization of the sigma 1 receptor was investigated in MDA-MB-231 cells by immunocytochemistry and confocal microscopy, expression was visualized predominantly at the cell periphery. We have tested the effect of sigma 1 and sigma 2 drugs and a sigma 1 receptor silencing construct on various aspects of the metastatic process on two breast cell lines of different metastatic potential and a normal breast cell line. Both sigma 1 and sigma 2 drugs and the sigma 1 receptor silencing construct had effects on proliferation and adhesion for breast cancer cell lines, compared to a non-cancerous breast cell line. This data suggests sigma 1 receptor plays a role in proliferation and adhesion of breast cancer cells. Therefore, it is likely to be a potential target for the diagnosis and therapy of breast cancer. (c) 2005 Elsevier Ireland Ltd. All rights reserved.