Abstract 274: PGC-1α over-expression is related to increased cell proliferation and tumorigenesis

Abstract

Abstract Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a coactivator interacting with multiple transcription factors and regulates several metabolic processes. Recent studies have focused on the role of several coactivators in cancer. Especially, a role of PGC-1α in cancer has been controversial. Some studies show that the expression level of PGC-1α decreased in certain cancer tissues and PGC-1α over-expression induces apoptosis in ovarian cancer cells. On the contrary, it has been found that PGC-1α promotes cell growth in prostate cancer cells, suggesting that PGC-1α may be involved in the pathogenesis of cancer. However, the molecular mechanism for it has not been clarified. Thus, the role of PGC-1α in the cell proliferation and tumorigenesis was evaluated using human embryonic kidney HEK293 cells that stably over-expressed PGC-1α. Forced expression of PGC-1α in HEK293 cells resulted in increased cell proliferation and anchorage-independent growth in soft agar. In addition, HEK293 cells that highly expressed PGC-1α enhanced tumor formation when these cells are subcutaneously injected into the bilateral flanks of immunodeficient Balb/c mice. To find out the molecular targets for increased proliferation and tumorigenesis by PGC-1α, GeneFishing DEG screening system was employed. As a result, one up-regulated gene (acyl-CoA binding protein; ACBP) was identified. Up-regulated ACBP expression was confirmed by Western blot and immunofluorescence microscopy. The expression of ACBP was decreased by PGC-1α siRNA transfection. These data suggest that the expression of ACBP may be related to the expression of PGC-1α. In addition, down-regulation of ACBP and PGC-1α by siRNA transfections resulted in the decreased cell proliferation. Taken together, these findings suggest that PGC-1α may promote cell proliferation and tumorigenesis. Thus, PGC-1α can be a good candidate for a molecular therapeutic target for cancers. However, the detailed molecular mechanisms for up-regulation of ACBP by PGC-1α are remained unresolved. Thus, further studies on the clarification of molecular interactions of ACBP and PGC-1α are needed. This study was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) through the Medical Research Center for Cancer Molecular Therapy at Dong-A University (R13-2002-044-05002-0). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 274. doi:10.1158/1538-7445.AM2011-274