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

  • Kim, Byung-Chul (Department of Biochemistry, College of Natural Sciences, Kangwon National University)
  • Published : 2008.10.31

Abstract

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.

Keywords

References

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