Understanding the role of insulin receptor substrate 1 (IRS1) dependent signal transduction network in development of glioblastoma multiforme in in vitro.

Glucose is the primary energy source in brain and it is extensively used in brain cells. Therefore, the brain performs its physiological role through the strict regulations of glucose metabolism. Insulin Receptor Substrate (IRS) proteins are the most important adapter proteins involved in the regulation of glucose metabolism. IRS1 is the most studied member of this family. It interacts with many cancer-related receptors and studies have shown that its overexpression is associated with many cancer types such as breast, lung, prostate and kidney. In addition to these cancer types, increased IRS1 expression has also been shown in medullablastoma is one of the central nervous tumors. Under the light of these studies, we thought that IRS1 expression might increase in Gliblastoma Multiforme (GBM) is one of the most important type of central nervous system tumors. Therefore, we aimed to figure out the role of IRS1 signaling network in the development of GBM. In this study, U-87 MG cell line was used. In order to increase the expression of IRS1 in GBM cells, U-87 MG cells were transfected with pcDNA3.1 flag-tagged-human IRS1 expression vector by lipofectamine. Functional and molecular effects of ectopic IRS1 overexpression on survival of GBM cells and insulin signaling were determined by MTT analysis and westen blotting, respectively. Our results suggested that ectopic IRS1 overexpression led a increase in cell survival. We also detected that expressions/activations of Grb2, ERK and AKT proteins increased through IRS1 overexpression in U-87 MG cells. Our study showed that increased IRS1 expression and activation promote cell viability via AKT activation. Keywords: Brain Tumors, Glioblastoma Multiforme, IRS1, Insulin Receptor Substrate Proteins (IRS), Insülin Signal.