PI 3-kinase/Akt and STAT3 are required for the prevention of TGF-β-induced Hep3B cell apoptosis by autocrine motility factor/phosphoglucose isomerase

Shih, Wen-Ling; Liao, Ming-Huei; Lin, Ping-Yuan; Chang, Chi-I; Cheng, Hsueh-Ling; Yu, Feng-Ling; Lee, Jeng-Woei

doi:10.1016/j.canlet.2009.09.014

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Volume 290, Issue 2 , Pages 223-237, 28 April 2010

PI 3-kinase/Akt and STAT3 are required for the prevention of TGF-β-induced Hep3B cell apoptosis by autocrine motility factor/phosphoglucose isomerase

Wen-Ling Shih
- Graduate Institute of Biotechnology, National Pingtung University of Science and Technology, Pingtung, Taiwan
- Corresponding author. Address: Graduate Institute of Biotechnology, National Pingtung University of Science and Technology, 1, Shuefu Rd., Neipu, Pingtung 91201, Taiwan. Tel.: +886 8 7703202x5192; fax: +886 8 7740550.
Ming-Huei Liao
- Department of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan
Ping-Yuan Lin
- Graduate Institute of Life Science, Tzu-Chi University, Hualien, Taiwan
Chi-I Chang
- Graduate Institute of Biotechnology, National Pingtung University of Science and Technology, Pingtung, Taiwan
Hsueh-Ling Cheng
- Graduate Institute of Biotechnology, National Pingtung University of Science and Technology, Pingtung, Taiwan
Feng-Ling Yu
- Department of Nursing, Tzu-Hui Institute of Technology, Pingtung, Taiwan
Jeng-Woei Lee
- Graduate Institute of Life Science, Tzu-Chi University, Hualien, Taiwan

Received 22 May 2009; received in revised form 16 September 2009; accepted 17 September 2009. published online 12 October 2009.

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-β-induced apoptosis, and demonstrated that AMF/PGI against TGF-β-induced apoptosis was correlated with its enzymatic activity. AMF/PGI did not alter TGF-β-receptor expression nor affect TGF-β-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-β-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.

Keywords: AMF/PGI, TGF-β, PI 3-kinase, Akt, STAT3