Related Experiment Video
Updated: Dec 27, 2025

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
Upregulation of PACE4 in prostate cancer is not dependent on E2F transcription factors
Anita Bakrania1,2,3, Mélanie Aubé4, Roxane Desjardins1,2,3
1Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
Abstract:
Recent studies in prostate cancer have identified PACE4, a proprotein convertase enzyme, as an emerging therapeutic target. Inhibition of PACE4-altCT, an oncogenic isoform of PACE4, using molecular or pharmacological approaches results in decreased cell proliferation and tumor progression in xenograft models. Although several validations have confirmed PACE4-altCT as a novel therapeutic target, the transcriptional regulation of PACE4 isoforms and mechanism of action remain a challenge. Previously, it has been reported that the human PACE4 promoter possesses potential binding sites for the E2F family of transcription factors, all of which are involved in cell cycle regulation and synthesis of DNA in mammalian cells. Therefore, we attempted to conduct in-depth evaluation of E2Fs on PACE4 and PACE4 isoform expression in prostate cancer. We conducted in vitro molecular silencing studies in various prostate cancer cell lines and determined the change in PACE4 expression levels. The results clearly show that the E2Fs alone do not alter PACE4 expression.
Insights
E2F transcription factors do not regulate PACE4 expression in prostate cancer. This finding challenges previous assumptions about the transcriptional control of this emerging therapeutic target, impacting future research directions.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Prostate cancer research identifies PACE4, a proprotein convertase, as a therapeutic target.
- The oncogenic PACE4-altCT isoform is implicated in tumor progression, with its inhibition showing promise in preclinical models.
- Transcriptional regulation of PACE4 isoforms remains poorly understood, despite its therapeutic relevance.
Purpose of the Study:
- To investigate the role of E2F transcription factors in regulating PACE4 and its isoforms in prostate cancer.
- To elucidate the mechanism of action and transcriptional control of PACE4 in the context of prostate cancer.
Main Methods:
- In vitro molecular silencing studies were performed in prostate cancer cell lines.
- PACE4 expression levels were analyzed following E2F manipulation.
Main Results:
- E2F transcription factors alone did not significantly alter PACE4 expression levels in the studied prostate cancer cell lines.
- This suggests that E2Fs are not the primary regulators of PACE4 expression in this context.
Conclusions:
- The study indicates that E2F transcription factors are not involved in the direct transcriptional regulation of PACE4 in prostate cancer.
- Further research is needed to identify the specific regulators of PACE4 and its isoforms to advance therapeutic strategies.
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Negative Regulator Molecules
Abnormal Proliferation
Cell Specific Gene Expression
Master Transcription Regulators
Regulation of Angiogenesis and Blood Supply

