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Glucocorticoid receptor β stimulates Akt1 growth pathway by attenuation of PTEN

Lance A Stechschulte1, Leah Wuescher2, Joseph S Marino3

  • 1From the Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology and.

The Journal of Biological Chemistry
|May 13, 2014
PubMed

Insights

Glucocorticoid receptor beta (GRβ) suppresses PTEN, enhancing insulin-stimulated growth by activating Akt1. This GRβ/Akt1 pathway promotes tumor growth independently of GRα.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cancer Research

Background:

  • Glucocorticoids (GCs) inhibit proliferation and induce apoptosis via the glucocorticoid receptor (GR).
  • The GR gene yields two isoforms: GRα (mediates GC effects) and GRβ (ligand-binding deficient).
  • GRβ's role in insulin signaling and growth pathways remained unclear.

Purpose of the Study:

  • To investigate the role of GRβ in insulin signaling and cellular growth.
  • To elucidate the molecular mechanisms by which GRβ influences growth pathways.

Main Methods:

  • Investigated GRβ's effect on PTEN expression.
  • Assessed GRβ's impact on insulin-stimulated Akt phosphorylation.
  • Determined GRβ's specific interactions within growth signaling pathways.

Main Results:

  • GRβ was found to suppress PTEN expression, leading to enhanced insulin-stimulated growth.
  • GRβ increased basal Akt phosphorylation, further amplified by insulin, specifically targeting Akt1.
  • These effects were independent of GRβ's known inhibitory actions on GRα.

Conclusions:

  • The GRβ/Akt1 axis is a significant mediator of insulin-stimulated growth.
  • GRβ promotes tumor growth by modulating the PTEN/Akt1 pathway.
  • Targeting the GRβ/Akt1 axis may offer novel therapeutic strategies in cancer treatment.
Keywords:
AktCell GrowthCell ProliferationGlucocorticoidGlucocorticoid ReceptorHormone ReceptorInsulinPhosphatase and Tensin Homolog (PTEN)

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