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KMID : 0624620080410100728
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BMB Reports
2008 Volume.41 No. 10 p.728 ~ p.732
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FoxO3a mediates transforming growth factor-β1-induced apoptosis in FaO rat hepatoma cells
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Kim Byung-Chul
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Abstract
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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-β1 (TGF-β1)-induced apoptosis in FaO rat hepatoma cells. TGF-β1 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-β1. In contrast, transfection with small-interfering RNA (siRNA) oligonucleotide specific for FoxO3a significantly inhibited caspase activation in FaO cells treated with TGF-β1. It thus appears that FoxO3a plays a crucial mediatory role in the TGF-β1 signaling pathway leading to apoptosis.
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KEYWORD
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Akt, Apoptosis, FoxO3a, Hepatoma cells, TGF-β1
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