PI 3-kinase/Akt and STAT3 are required for the prevention of TGF-beta-induced Hep3B cell apoptosis by autocrine motility factor/phosphoglucose isomerase.
We established Hep3B cells stably-expressing wild-type and mutated AMF/PGI with differing enzymatic activities in order to investigate how AMF/PGI affects TGF-beta-induced apoptosis, and demonstrated that AMF/PGI against TGF-beta-induced apoptosis was correlated with its enzymatic activity. AMF/PGI did not alter TGF-beta-receptor expression nor affect TGF-beta-induced PAI-1 gene promoter or Smad3/4 activity. AMF/PGI induced PI 3-kinase activity, IRS and Akt phosphorylation, which can further regulate BAD phosphorylation. Constitutively-active p110 enhanced AMF/PGI-mediated anti-apoptosis activity, and dominant negative Akt alleviated anti-TGF-beta-induced apoptosis. We also demonstrated that STAT3 is a weak anti-apoptotic agent but has an increased anti-apoptotic effect in cooperation with PI 3-kinase/Akt.
Shih
Wen-Ling
WL
National Pingtung University of Science and Technology, Taiwan. wlshih@mail.npust.edu.tw
Liao
Ming-Huei
MH
Lin
Ping-Yuan
PY
Chang
Chi-I
CI
Cheng
Hsueh-Ling
HL
Yu
Feng-Ling
FL
Lee
Jeng-Woei
JW
D017209:Apoptosis / Q000502:physiology*; D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002469:Cell Separation; D005434:Flow Cytometry; D015870:Gene Expression; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D050796:STAT3 Transcription Factor; D016212:Transforming Growth Factor beta; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005956:Glucose-6-Phosphate Isomerase