Inhibition of Glycogen Synthase Kinase-3β Counteracts Ligand-Independent Activity of the Androgen Receptor in Castration Resistant Prostate Cancer
2011

Inhibition of GSK-3β Reduces Androgen Receptor Activity in Prostate Cancer

publication 10 minutes Evidence: moderate

Author Information

Author(s): Vladislav V. Glinsky, Stefanie V. Schütz, Andres J. Schrader, Friedemann Genze, Felicitas Cronauer, Marcus V. Schrader

Primary Institution: University of Missouri-Columbia

Hypothesis

Inhibition of glycogen synthase kinase-3β (GSK-3β) will reduce the activity of the androgen receptor (AR) in castration-resistant prostate cancer (CRPC) cells.

Conclusion

Inhibition of GSK-3β leads to a reduction in nuclear localization of the androgen receptor and diminishes its activity in CRPC cells.

Supporting Evidence

  • Inhibition of GSK-3β resulted in a significant decrease in nuclear AR levels in CRPC cell lines.
  • AR-positive CRPC cells were more susceptible to growth inhibition by GSK-3β inhibitors compared to AR-negative cells.
  • Long-term inhibition of GSK-3β led to a decrease in AR protein levels in C4-2 cells.

Takeaway

This study shows that blocking a specific protein can help move a cancer-related protein out of the cell's nucleus, which may help treat prostate cancer that doesn't respond to regular treatments.

Methodology

The study used in vitro and in vivo experiments to analyze the effects of GSK-3β inhibition on AR activity in prostate cancer cell lines.

Potential Biases

Potential bias may arise from the use of specific cell lines that may not reflect the heterogeneity of prostate cancer.

Limitations

The study primarily focuses on specific cell lines and may not fully represent the complexity of prostate cancer in patients.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0025341

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