Acta Pharmacologica Sinica (2009) 30: 113-119; doi: 10.1038/aps.2008.8; published online 8th December 2008

Insulin-like growth factor-1 promotes cell cycle progression via upregulation of cyclin D1 expression through the phosphati­dy­linositol 3-kinase/nuclear factor-κB signaling pathway in FRTL thyroid cells

Aim: Insulin-like growth factor-1 (IGF-1) is an important hypertrophic and cell cycle progression factor for a number of cell types.  It has been proven that IGF-1 is involved in the regulation of thyroid proliferation and cell cycle progression; however, the exact mechanism of this regulation has not been fully elucidated.  In the present study, we investigated the effect of IGF-1 on the expression of cyclin D1, an important cell cycle regulatory protein, and a signaling pathway involved in IGF-1’s effect on cyclinD1 expression in FRTL thyroid cells.    

Methods: FRTL thyroid cells were treated with IGF-1 or vector control for 24 h.  As appropriate to individual experiments, a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, and/or a nuclear factor-κB (NF-κB) inhibitor, BAY11-7082, were added 1 h prior to IGF-1 treatment.  Western blotting was used to detect cyclin D1 protein expression.  Immunofluorescence was performed to analyze the expression of IκBα, an NF-κB inhibitory protein.  Cell cycle analysis was performed by fluorescence activated cell sorting (FACS).

Results: IGF-1 increased the cyclin D1 expression in thyroid cells.  This increase was blocked by pretreatment with LY294002 or BAY11-7082.  Further studies showed that IGF-1 specifically induced NF-κB activity.  Treatment with IGF-1 could accelerate cell cycle progression from G0/G1 to S phase, whereas this progression was inhibited by the presence of LY294002 or BAY11-7082.

Keywords: insulin-like growth factor-1; phosphatidylinositol 3-kinase; nuclear factor- κB; cyclin D1