RESUMEN
BACKGROUND AND PURPOSE: Proteasome inhibitors exhibit cytotoxic against tumours of different histology. However, the mechanism of apoptosis induction by these compounds remains unclear and is likely to be a complex cascade of events. Bcl-2-associated athanogene (BAG) family proteins are characterized by their property of interaction with a variety of partners involved in modulating the proliferation/death balance, including heat shock proteins (HSP), Bcl-2, Raf-1. The role of BAG family proteins in proteasome inhibition has not been elucidated. EXPERIMENTAL APPROACH: Effects of proteasome inhibitors on BAG2 expression were evaluated using real-time reverse transcription-polymerase chain reaction (RT-PCR). BAG2 expression was knocked down by small interfering RNAs (siRNA). Cell death was evaluated using Annexin V/propidium iodide staining and subsequent FACS. KEY RESULTS: The proteasome inhibitors, MG132, PSI, lactacystin and epoxomicin, induced BAG2 at the transcriptional level. MG132-induced apoptosis was significantly suppressed by BAG2 knockdown using RNA interference. CONCLUSIONS AND IMPLICATIONS: Our results suggest that BAG2 is a novel molecule induced by proteasome inhibition, which exhibits a pro-apoptotic property in death of thyroid cancer cells induced by proteasome inhibition.
