Phosphatidylinositol 3-kinase (PI3K) signalling regulates insulin-like-growth factor binding protein-2 (IGFBP-2) production in human adipocytes

Abstract Objective Insulin-like-growth factor binding protein 2 (IGFBP-2) is thought to be a marker for the phosphatase and tensin homolog (PTEN) status and activity of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. We aimed to evaluate whether or not lipoma cells of a patient with a heterozygous deletion in the PTEN gene would produce more IGFBP-2 than PTEN non deficient control cells. Moreover, we analysed the influence of pharmacological inhibitors of the PI3K/AKT/mTOR pathway on IGFBP-2 production. Design PTEN deficient preadipocytes and control PTEN non deficient preadipocytes were differentiated in vitro and treated with the respective inhibitors. PTEN was transiently down regulated by siRNA in human preadipocytes. IGFBP-2 mRNA and protein expression and IGFBP-2 in culture supernatant were measured. Results PTEN deficient lipoma cells were found to produce IGFBP-2 during in vitro differentiation in comparable amounts to PTEN non deficient cells. In contrast, acute down regulation of PTEN in preadipocytes resulted in enhanced production of IGFBP-2. Incubation with the PI3K inhibitors LY294002 and wortmannin decreased IGFBP-2 mRNA and protein. Neither the mTOR complex 1 inhibitor rapamycin nor PD98059, an inhibitor of MEK (mitogen-activated protein kinase kinase), showed a significant effect on IGFBP-2 production. Conclusion IGFBP-2 production in PTEN deficient preadipocytes was not influenced by PTEN deficiency or by inhibition of mTORC1 and MAPK. In contrast, inhibition of PI3K decreased IGFBP-2 expression and secretion.