Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) upregulated E-cadherin expression in HepG2 cells

Lee, Hui-Ju; Su, Yeu; Lui, Wing-Yiu; Chau, Gar-Yang; Yin, Pen-Hui; Lee, Hsin-Chen; Chi, Chin-Wen

doi:10.1016/j.febslet.2008.01.033

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Volume 582, Issue 5 , Pages 627-634, 5 March 2008

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) upregulated E-cadherin expression in HepG2 cells

Edited by Laszlo Nagy

Hui-Ju Lee
- Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, ROC
- Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 112, Taiwan, ROC
Yeu Su
- Institute of Biopharmaceutical Science, School of Life Science, National Yang-Ming University, Taipei 112, Taiwan, ROC
Wing-Yiu Lui
- Department of Surgery, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, ROC
- Department of Surgery, Taipei Veterans General Hospital, Taipei 112, Taiwan, ROC
Gar-Yang Chau
- Department of Surgery, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, ROC
- Department of Surgery, Taipei Veterans General Hospital, Taipei 112, Taiwan, ROC
Pen-Hui Yin
- Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 112, Taiwan, ROC
Hsin-Chen Lee
- Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, ROC
- Corresponding authors. Address: Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 112, Taiwan, ROC. Fax: +886 2 28751562 (C.-W. Chi).
Chin-Wen Chi
- Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan, ROC
- Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 112, Taiwan, ROC
- Corresponding authors. Address: Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 112, Taiwan, ROC. Fax: +886 2 28751562 (C.-W. Chi).

Received 21 November 2007; received in revised form 9 January 2008; accepted 22 January 2008. published online 31 January 2008.

Abstract

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), a highly inducible transcriptional coactivator regulating energy homeostasis, is down-regulated in hepatoma tissues. To dissect its role in hepato-tumorigenesis, Ingenuity^® Pathway Analysis was applied to construct pathways affected by PGC-1α upregulation in HepG2 hepatoma cells based on our microarray data. Interestingly, migration of these cells was markedly diminished by PGC-1α overexpression in consistency with Ingenuity^® results. Moreover, a deduced expression increase of E-cadherin was also observed in PGC-1α-overexpressing HepG2 cells. Finally, transient transfection and chromatin-immunoprecipitation assays suggested that increased histone acetylation might be responsible for PGC-1α-mediated transactivation of a minimal E-cadherin promoter.

Abbreviations: ChIP, chromatin-immunoprecipitation, GFP, green fluorescence protein, HAT, histone acetyltransferase, HCC, hepatocellular carcinoma, MOI, multiplicity of infection, PGC-1α, peroxisome proliferator-activated receptor gamma coactivator-1 alpha, PPAR, peroxisome proliferator-activated receptor, ROS, reactive oxygen species, SEAP, secreted alkaline phosphatase