FoxO3a mediates transforming growth factor-β1-induced apoptosis in FaO rat hepatoma cells

FoxO3a is a member of the forkhead box class O (FoxO) transcription factor family and an important regulator of apoptosis. This work aimed to elucidate the involvement of FoxO3a in transforming growth factor-beta 1 (TGF-beta 1)-induced apoptosis in FaO rat hepatoma cells. TGF-beta 1 caused a time-dependent activation of FoxO3a and a subsequent increase in FoxO response-element-containing luciferase reporter activity, which was Akt-sensitive. The FaO cells stably transfected with a wild type FoxO3a were more susceptible to the formation of apoptotic bodies, populations of sub-G1 apoptotic cells, and collapse of the mitochondrial-membrane potential triggered by TGF-beta 1. In contrast, transfection with small-interfering RNA (siRNA) oligonucleotide specific for FoxO3a significantly inhibited caspase activation in FaO cells treated with TGF-beta 1. It thus appears that FoxO3a plays a crucial mediatory role in the TGF-beta 1 signaling pathway leading to apoptosis. [BMB reports 2008; 41(10): 728-732]