Role of ERβ and EGFR in Prostate Cancer: Therapeutic Implications
Posted: Monday, May 24, 2021
Knockout of estrogen receptor beta (ERβ) is known to increase nuclear expression of EGFR in the prostate in mice, a predictor of poor outcome; however, adding ERβ agonists to abiraterone therapy in humans may sustain expression of ERβ and offer potential benefit to patients. Jan-Ake Gustafsson, MD, PhD, of the Karolinska Institutet in Huddinge, Sweden, and colleagues reported these findings in the journal PNAS.
Researchers utilized four different cohorts of men to examine the role of ERβ in the human prostate. Group one was a Swedish cohort of men with normal prostates and men with prostate cancer. Group two contained men with benign prostatic hyperplasia (BPH) treated with finasteride with or without an ERβ agonist. Group three consisted of men with prostate cancer above Gleason grade 4 treated with abiraterone and androgen-deprivation therapy (ADT). Group four consisted of men with prostate cancer above Gleason grade 4 on ADT with or without androgen receptor blockade. Samples were analyzed by immunohistochemistry.
In patients with BPH receiving no therapy, EGFR was mostly expressed on the cell membrane of epithelial cells. When patients were treated with finasteride, many cells with EGFR were present in the nucleus; however, when an ERβ agonist was added to finasteride, EGFR was rarely seen in the nucleus.
In the normal prostate, ERβ was expressed; however, its expression was diminished in Gleason grade 3 prostate cancer and was not seen in Gleason grade 5 prostate cancer samples. Similarly, EGFR was expressed on the cell membrane in normal prostate samples, and nuclear expression of EGFR increased with increasing Gleason grade. In addition, researchers noted that the recurrence rate of prostate cancer appeared to be higher with nuclear EGFR (79%) than with nuclear EGFR-negative disease (43%).
ERβ expression was measured among patients treated with abiraterone for different lengths of time. Short-term treatment was found to increase ERβ expression, whereas treatment for longer than 7 months led to the loss of ERβ expression in prostate cancer. This suggests a window in prostate cancer treatment where ERβ agonists may be effective via prevention of EGFR nuclear translocation.
Disclosure: The study authors reported no conflicts of interest.
