Neural Transcription Factor: Driver for Castration-Resistant Prostate Cancer?
Posted: Thursday, February 20, 2020
Researchers from the Medical College of Georgia at Augusta University have identified a common neural transcription factor—BRN4—as a driver for castration-resistant prostate cancer. Although BRN4 has been mostly expressed in the central nervous system and the inner ear, investigators now have evidence of its amplification and overexpression in patients with neuroendocrine prostate cancer. Their findings were published in Clinical Cancer Research.
“We are showing that BRN4 does have a role in driving neuroendocrine differentiation in prostate cancer, and it does have a role in prostate cancer,” stated first study author and cancer biologist Divya Bhagirath, PhD, in a Medical College of Georgia press release.
The researchers used clinical samples of castration-resistant prostate cancer with either adenocarcinoma features or neuroendocrine features and nonmalignant prostate epithelial cell lines in their study. The authors cultured castration-resistant prostate cancer with adenocarcinoma features in the presence of enzalutamide to demonstrate differentiation of cells into neuroendocrine prostate cancer. They then identified potential candidate drivers by examining genes with copy number alterations in prostate cancers with adenocarcinoma features as well as neuroendocrine features.
Using real-time polymerase chain reaction and western blot analysis, the researchers identified 5x to 20x increased expression of BRN4 in the castration-resistant prostate cancer with neuroendocrine features (P < .05). The authors further identified that upregulation of BRN4 seemed to increase the relative migration and invasiveness of the tumors compared with controls (P < .005). They then focused on the role of extracellular vesicles in adaptation of prostate cancer to enzalutamide. Uptake of extracellular vesicles containing BRN2 and BRN4 in prostate cancer cells treated with enzalutamide was demonstrated.
This study identifies BRN4 as a driver for castration-resistant prostate cancer, which could be used as a potential target for future clinical studies.
Disclosure: The study authors reported no conflicts of interest.
