title: PI 3-kinase/Akt and STAT3 are required for the prevention of TGF-beta-induced Hep3B cell apoptosis by autocrine motility factor/phosphoglucose isomerase.
abstract: 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.
authors.affiliation: National Pingtung University of Science and Technology, Taiwan. wlshih@mail.npust.edu.tw
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Shih
authors.forename: Ming-Huei
authors.initials: MH
authors.lastname: Liao
authors.forename: Ping-Yuan
authors.initials: PY
authors.lastname: Lin
authors.forename: Chi-I
authors.initials: CI
authors.lastname: Chang
authors.forename: Hsueh-Ling
authors.initials: HL
authors.lastname: Cheng
authors.forename: Feng-Ling
authors.initials: FL
authors.lastname: Yu
authors.forename: Jeng-Woei
authors.initials: JW
authors.lastname: Lee
mesh_terms: 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*
chemical_list: D050796:STAT3 Transcription Factor; D016212:Transforming Growth Factor beta; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005956:Glucose-6-Phosphate Isomerase