FoxO3a mediates transforming growth factor-beta1-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-beta1 (TGF-beta1)-induced apoptosis in FaO rat hepatoma cells. TGF-beta1 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-beta1. In contrast, transfection with small-interfering RNA (siRNA) oligonucleotide specific for FoxO3a significantly inhibited caspase activation in FaO cells treated with TGF-beta1. It thus appears that FoxO3a plays a crucial mediatory role in the TGF-beta1 signaling pathway leading to apoptosis.
Kim
Byung-Chul
BC
Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Korea. bckim@kangwon.ac.kr
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015533:Transcriptional Activation / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D053773:Transforming Growth Factor beta1