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09:43
Isolation, Culture, and Characterization of Prostate Cancer-Associated Fibroblasts
Published on: August 1, 2025
663
BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration
Carolyn J Loveridge1,2, Sarah Slater2, Kirsteen J Campbell1,2
1Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden, Glasgow, G61 1QH, UK.
Oncogene
|November 20, 2019
Summary
Elevated BRF1 levels in prostate cancer correlate with poor prognosis and accelerated tumor growth. BRF1 impacts immune cell infiltration and complement system components, suggesting therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- BRF1 is a key regulator of RNA Polymerase III transcription.
- Elevated BRF1 levels are observed in various cancers.
- The role of BRF1 in prostate cancer progression is not fully understood.
Purpose of the Study:
- To investigate the association between BRF1 expression and prostate cancer prognosis.
- To elucidate the functional role of BRF1 in prostate cancer development and progression.
- To explore the impact of BRF1 on the tumor microenvironment, including immune responses and the complement system.
Main Methods:
- Analysis of BRF1 levels in human prostate cancer tissues.
- In vitro studies using prostate cancer cell lines to assess the effects of BRF1 overexpression and downregulation on cell proliferation and cell cycle.
- Utilizing a genetically engineered mouse model (PtenΔ/Δ BRF1Tg) of prostate cancer.
- Proteomic analysis of cell secretomes to identify differentially expressed proteins.
- Immunohistochemical analysis of tumor tissues to assess immune cell infiltration and complement component levels.
Main Results:
- High BRF1 levels in human prostate cancer correlate with poor patient prognosis.
- BRF1 overexpression enhances prostate cancer cell proliferation and accelerates carcinogenesis in a mouse model.
- BRF1 dysregulation alters immune cell infiltration, reducing neutrophils and CD4+ T cells in tumors.
- Decreased levels of complement factor D (CFD) and C7 were observed in BRF1-overexpressing tumors and cell secretomes.
- Low C7 expression significantly correlates with poor prognosis in human prostate cancer.
Conclusions:
- BRF1 is a significant driver of prostate cancer progression and is associated with poor clinical outcomes.
- BRF1 influences tumor immunity by modulating the complement system and immune cell infiltration.
- Targeting BRF1 or components of the complement pathway may offer novel therapeutic strategies for prostate cancer.
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