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Stepping stones in the path of glucocorticoid-driven apoptosis of lymphoid cells

E Brad Thompson1

  • 1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555-1068, USA. bthompso@utmb.edu

Acta Biochimica Et Biophysica Sinica
|July 8, 2008
PubMed

Insights

Glucocorticoid (GC) sensitivity in lymphoid cells hinges on active GC receptors and interplay with cell signaling pathways. Identifying a core gene network is crucial for testing GC-responsive hematologic malignancies.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Glucocorticoids (GCs) regulate gene expression in lymphoid cells, influencing apoptosis.
  • GC-induced apoptosis requires active GC receptors and interaction with key cell signaling pathways.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying GC-regulated apoptosis in lymphoid cells.
  • To identify a core network of GC-controlled genes in GC-sensitive malignant cells.

Main Methods:

  • Analysis of gene regulation by GCs in lymphoid cell cultures.
  • Investigating the interaction between GC receptors and major cell signaling pathways (MAPK, cAMP/PKA, hedgehog, mTOR, c-myc).

Main Results:

  • Apoptotic sensitivity to GCs is dependent on active GC receptors.
  • Interactions with multiple cell signaling pathways modulate GC-driven apoptosis.
  • A conserved core of GC-regulated genes exists in many malignant, GC-sensitive cells.

Conclusions:

  • The balance of cell signaling pathways dictates GC-induced apoptosis.
  • The identified core gene list warrants validation in clinical hematologic malignancy samples.

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