Loss of Glucocorticoid Receptor Expression by DNA Methylation Prevents Glucocorticoid Induced Apoptosis in Human Small Cell Lung Cancer Cells
2011

Loss of Glucocorticoid Receptor Expression in Small Cell Lung Cancer

Sample size: 14 publication Evidence: moderate

Author Information

Author(s): Kay Paul, Schlossmacher George, Matthews Laura, Sommer Paula, Singh Dave, White Anne, Ray David

Primary Institution: University of Manchester

Hypothesis

The loss of glucocorticoid receptor (GR) expression in small cell lung cancer (SCLC) cells is due to DNA methylation.

Conclusion

DNA methylation decreases GR gene expression in human SCLC cells, which may contribute to their resistance to glucocorticoids.

Supporting Evidence

  • GR expression is lower in SCLC cells compared to non-SCLC cells.
  • Reversal of GR gene methylation increased GR expression in SCLC cells.
  • Increased GR expression restored glucocorticoid sensitivity in SCLC cells.
  • Significant correlation between GR promoter methylation and GR protein expression was observed.
  • Treatment with a DNA methyltransferase inhibitor led to increased apoptosis in SCLC cells.

Takeaway

In small cell lung cancer, a chemical change in DNA makes it hard for cells to use a protein that helps them die when they should, which can make the cancer grow faster.

Methodology

The study involved examining GR promoter methylation in SCLC cell lines and assessing GR expression after treatment with a DNA methyltransferase inhibitor.

Limitations

The study primarily focused on in vitro cell lines, which may not fully represent in vivo conditions.

Participant Demographics

The study used human SCLC cell lines derived from patients with pathologically confirmed SCLC.

Statistical Information

P-Value

p=0.01

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0024839

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication