Loss of Glucocorticoid Receptor Expression in Small Cell Lung Cancer
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)
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