The Role of Sigma Receptor in Breast Cancer

Abstract : We completed specific tasks #1 and #2 and have published the results (Breast Cancer Res Treat 87:205-214, 2004). We also extended the SiR mRNA correlative studies to gene expression data obtained from 600 breast cancers. There continued to be no consistent correlation between SiR mRNA expression and prognosis or lymph node or estrogen receptor status. However the data confirmed frequent mRNA expression of SiR in breast cancer. Progress has been made in task #3. Eleven breast cancer cell lines were screened for SiR expression with Western blot and one cell line T47D were negative. This cell line was successfully transfected with SIR using PcDNA 3.1 construct. No change in cell proliferation, apoptosis or sensitivity to chemotherapy was seen at baseline or after SiR ligand (SKF 10047) exposure. This was consistent with the negative results previously observed in SiR-positive cell lines treated with SKF 10047. SiR appears to play a role in regulating cell migration. SKF 10047 inhibits migration of MDA 231 and MDA 435 cells in vitro. Gene expression analysis after exposure to SKF 10047 suggests that this compound inhibits small UTPase-mediated signaling pathways. We are currently examining the molecular mechanism of SiR mediated inhibition of cell migration by measuring the activity of Rho, Rac and CDC42 before and after SKF 10047 exposure. We are also in the process of developing SiR knock down cells by using siRNA technology.