INVESTIGADORES
ABBA Martin Carlos
congresos y reuniones científicas
Título:
RHBDD2 silencing and gene expression profiling of breast cancer cells identify a signature associated to apoptosis modulation
Autor/es:
ABBA MC; CANZONERI R; PELLON-MAISON M; ALDAZ CM; LACUNZA E
Lugar:
Bariloche
Reunión:
Simposio; The Second South American Spring Symposium in Signal Transduction and Molecular Medicine; 2012
Resumen:
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-GeneTM 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 breast 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 phenotype of 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 the modulation of the programmed cell
death in cancer cells.