Abstract B61: Phospholipid scramblase is a critical mediator of estrogen-induced apoptosis in antihormone resistant breast cancer cells

Abstract

Abstract Phospholipid scramblase 1 (PLSCR1) is a mutiply palmitoylated protein which is localized in either the cell membrane or nucleus depending on its palmitoylated state and is responsible for the translocation of phospholipids between the two monolayers of a lipid bilayer of a cell membrane in a calcium (Ca2+)-dependent manner. There is evidence that PLSCR1 plays a role in cell signaling and apoptosis. In the present study, we investigated the functions of PLSCR1 in hormone-sensitive MCF-7 and T47D breast cancer cells versus antihormone-resistant MCF-7:5C and MCF-7:2A cells. We found that PLSCR1 protein and mRNA levels were dramatically increased in MCF-7:5C and MCF-7:2A cells compared to parental MCF-7 and T47D cells and suppression of PLSCR1 in these cells using small interfering RNA (siRNA) reduced their growth rate and altered their morphology to become more differentiated and spindle-shaped. Suppression of PLSCR1 also completely blocked estrogen-induced apoptosis in MCF-7:5C cells. Furthermore, we found that stable expression of PLSCR1 in MCF-7 cells enhanced their sensitivity to etoposide-induced apoptosis and that treatment of these cells with interferon-alpha 2 (IFN- 2) resulted in cell cycle arrest. Overall, these data show that PLSCR1 is overexpressed in antihormone-resistant breast cancer cells and they suggest that PLSCR1 plays an important role in sensitizing these cells to estrogen-induced apoptosis. These data also shed new insights into the biological and biochemical functions of PLSCR1 in breast cancer. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B61.