The Dual Role of Glucocorticoid Receptor in Prostate Cancer Progression

A recent study conducted by researchers at the University of Eastern Finland highlights the complex and dualistic role of the glucocorticoid receptor (GR) in prostate cancer. This hormone receptor, which influences gene expression through DNA binding, can both promote and inhibit tumor growth depending on specific cellular conditions.

Glucocorticoids are steroid hormones widely used as medications due to their potent anti-inflammatory effects. They exert their influence primarily through the glucocorticoid receptor, impacting various bodily functions. Simultaneously, the androgen receptor (AR) plays a central role in prostate cancer development and progression, with many therapies aiming to inhibit AR activity. However, resistance to such treatments often develops, and the glucocorticoid receptor has been identified as a key contributor to this resistance, capable of substituting for the androgen receptor and promoting cancer cell survival.

Previous research on GR in prostate cancer has focused on its potential oncogenic effects, especially in contexts where AR activity is suppressed. Yet, the new study by the Paakinaho Lab, published in Genome Research, reveals a more nuanced interaction between AR and GR. Using advanced genome-wide sequencing and single-cell analysis techniques, the researchers found that simultaneous activation of both receptors significantly enhances the binding of GR to specific DNA regions. This increased binding relies on active AR signaling, which facilitates genomic access for GR.

Interestingly, when AR is not activated, GR's ability to bind to these regions diminishes, altering gene regulation patterns. The combined activation of AR and GR synergistically influences gene transcription, notably enhancing the expression of tumor suppressor genes. Bioinformatics analysis with patient data suggests that increased expression of these protective genes correlates with better survival outcomes in prostate cancer patients.

This research indicates that GR's role in prostate cancer is context-dependent—acting as an oncogenic factor when AR is inactive but potentially exerting tumor-suppressive effects when AR activity is present. Consequently, the glucocorticoid receptor can be considered a double-edged sword: promoting treatment resistance under certain conditions yet also helping to restrain tumor growth in others.

Understanding the complex interplay between AR and GR is crucial for developing more effective therapies. Harnessing this knowledge could lead to new strategies that mitigate resistance and improve patient prognosis. As Dr. Paakinaho emphasizes, "It is vital to understand how this crosstalk can be leveraged in treatment development."

For further details, see the full study by Johannes Hiltunen et al. in Genome Research (2025).