Overexpression of bax induces down-regulation of store-operated calcium entry in prostate cancer cells

✍ Scribed by Na Li; Lin Zheng; Peihui Lin; David Danielpour; Zui Pan; Jianjie Ma

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 259 KB
• Volume: 216
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.21385

✦ Synopsis

Abstract

Store‐operated Ca^2+^ channels control homeostasis between extracellular Ca^2+^ reservoir and intracellular Ca^2+^ storage and play important roles in apoptosis in a wide variety of cells, including prostate epithelia. Recent studies have shown that the acquired apoptosis‐resistant nature of androgen‐independent prostate cancer is associated with reduced function of store‐operated Ca^2+^ entry (SOCE). This study investigates the functional interaction between Bax and SOCE in the apoptosis signaling cascade in prostate cancer. Our previous findings show that NRP‐154, an androgen‐independent prostate cancer cell line, could sustain overexpression of exogenous Bax without undergoing apoptosis. Here we show that sustained overexpression of Bax in NRP‐154 cells leads to down‐regulation of SOCE and reduced Ca^2+^ storage inside the endoplasmic reticulum. While reduced SOCE may represent an adaptive mechanism for cell survival, increased levels of Bax in the latent state enhances the sensitivity of NRP‐154 cells to TGF‐β and thapsigargin‐induced apoptosis. This enhanced apoptosis can be reduced by 2‐aminoethoxydiphenyl borate (2‐APB), an inhibitor of SOCE, or reversed under conditions where SOCE is only partially activated. Our results demonstrate a functional interaction between Bax and SOCE in apoptosis of prostate cancer, and support the concept that improving this interaction has therapeutic implications for prostate cancer. J. Cell. Physiol. 216: 172–179, 2008. © 2008 Wiley‐Liss, Inc.