Abstract 5265: Akt regulates insulin-like growth factor binding protein-3 by modulating its expression in human non-small cell lung cancer cells.

Abstract

Abstract Since it has been suggested the insulin-like growth factor (IGF)-independent antitumor effect of insulin-like growth factor binding protein-3 (IGFBP-3) in human cancer cells, the mechanism underlying the regulation of IGFBP-3 in the cells has not been fully studied. Therefore, in this study, we investigated the precise role of Akt in the regulation of cellular IGFBP-3 in human lung cancer cells. Inhibition of PI3K/Akt by siRNA transfection targeting Akt or by treatment with an inhibitor (LY294002) enhanced antiproliferative and proapoptotic effects of IGFBP-3 in lung cancer cells. Additional pharmacological (by using a small molecule inhibitor) or genomic (by siRNA-based silencing of PTEN or overexpression of dominant-negative Akt) approaches suggest that Akt regulates the expression and stability of IGFBP-3 protein. Further characterization of the role of Akt in the regulation of IGFBP-3 by introduction of constitutively active form of each Akt subtype indicates that Akt3 destabilized cellular IGFBP-3 and suppressed retinoic acid-induced IGFBP-3 expression in both TSC2-/- MEF and H226B lung cancer cells. Collectively, these data suggest a novel function of Akt, especially Akt3, as a negative regulator of IGFBP-3 and, further, the possible implication of combined treatment targeting IGFBP-3 and Akt in the treatment of lung cancer. Citation Format: Quanri Jin, Hye-Young Min, Young Mi Whang, Yeul Hong Kim, Ho-Young Lee. Akt regulates insulin-like growth factor binding protein-3 by modulating its expression in human non-small cell lung cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5265. doi:10.1158/1538-7445.AM2013-5265