IGFBP‐2 Expression in MCF‐7 Cells is Regulated by the PI3K/AKT/mTOR Pathway through Sp1 Induced Increase in Transcription

Abstract

Insulin‐like growth factor binding protein 2 (IGFBP‐2) has been implicated in the pathophysiology of neoplasia. The PI3K/AKT/mTOR pathway has recently been implicated as a predominant regulator of IGFBP‐2 at the protein level in MCF‐7 breast cancer cells.ObjectiveTo elucidate the specific molecular mechanisms that underlie this regulation.ResultsWe show that the PI3K/AKT/mTOR pathway regulates IGFBP‐2 protein levels by modulating IGFBP‐2 mRNA abundance in MCF‐7 cells. This change is achieved by regulating transcription through a critical region present in the first 200 bp upstream of the transcription initiation site where Sp1 transcription factor binds and drives transcription. Manipulations of the PI3K/AKT/mTOR pathway lead to changes in posttranslational modifications and nuclear abundance of Sp1 transcription factor.Methods usedQRT‐PCR, ELISA, Western Blot, Luciferase reporter assays, Immunofluorescence, Chromatin immunoprecipitation.ConclusionThis work provides a mechanistic explanation for the observed effects of the PI3K/AKT/mTOR pathway on IGFBP‐2 levels in MCF‐7 cells.Matei Mireuta was supported by the graduate studentship from the Weekend to End Breast Cancer of the Jewish General Hospital Foundation.