RHBDD2 silencing and gene expression profiling of breast cancer cells identify a signature associated to apoptosis modulation

ABBA MC; CANZONERI R ; PELLON-MAISON M; ALDAZ CM; LACUNZA E

Simposio; SISTAM 2012 The Second South American Spring Symposium in Signal Transduction and Molecular Medicine; 2012

In previous studies, we identified a distantly related rhomboid homologue gene known as RHBDD2( Rhomboid domain containing 2) to be markedly overexpressed in the advanced stages of the breast and colorectal cancer diseases. In order to identify RHBDD2 modulated pathways, we analyzed two breast cancer cell lines (MCF7 and T47D) from control and RHBDD2- siRNA transient gene silencing followed by gene expression profiling analysis using the whole genome Toray 3D-Gene TM Human Oligo Chip. Statistical analysis of the Toray's 3D gene expression profiling data identified 566 commonly differentially expressed genes in association to the RHBDD2 knockdown in both breas t cancer cell lines. Among the statistically significant over-represented biological processes, we identified apoptosis, cell cycle and response to DNA damage related genes. In addition, genes of the ubiquitin-proteasome and oxidative phosphorylation processes were also highly represented in the deregulated gene list. We further used a lentivirus-based system (shRNA-pLKO.1) for stable silencing of RHBDD2 mRNA in the T47D breast cancer cell line. Using a staurosporine-induced apoptosis model, we demonstrate that RHBDD2 abrogation resulted in an apoptosis-resistant phenotypeof T47D breast cancer cell line. These data are in line with a recent study, suggesting that RHBDD2 expression could be up-modulated in response to 5FU-induced apoptosis in colorectal cancer cells. Taken together, these data suggest that RHBDD2 could be involved in t he modulation of the programmed cell death in cancer cells