TGF-β and Its Role in Prostate Cancer Progression
Author Information
Author(s): Zhang Qiang, Chen Lin, Helfand Brian T., Jang Thomas L., Sharma Vidit, Kozlowski James, Kuzel Timothy Michael, Zhu Lihua J., Yang Ximing J., Javonovic Borko, Guo Yinglu, Lonning Scott, Harper Jay, Teicher Beverly A., Brendler Charles, Yu Nengwang, Catalona William J., Lee Chung
Primary Institution: Northwestern University Feinberg School of Medicine
Hypothesis
TGF-β may induce the expression of DNMTs in prostate cancer, which is associated with aggressive capabilities and disease recurrence.
Conclusion
The study found that TGF-β induces DNMT expression in prostate cancer, correlating with aggressive disease and predicting recurrence after surgery.
Supporting Evidence
- More aggressive prostate cancer cells had significantly higher TGF-β levels and increased DNMT expression.
- Blockade of TGF-β signaling decreased DNMT expression and increased TβR expression.
- Inhibition of TGF-β in a mouse model reduced tumor growth and DNMT levels.
- Increased DNMT1 expression was associated with biochemical recurrence after surgery.
- High levels of TGF-β and DNMTs correlated with higher Gleason grades in prostate cancer patients.
Takeaway
This study shows that a substance called TGF-β can make prostate cancer cells more aggressive by changing their DNA, which can help doctors predict if the cancer will come back after treatment.
Methodology
The study used human prostate cancer cell lines and a mouse model to investigate the effects of TGF-β on DNMT expression and cancer progression.
Potential Biases
Potential conflicts of interest due to involvement of authors with Genzyme Corporation.
Limitations
The study primarily focused on in vitro and in vivo models, which may not fully replicate human disease complexity.
Participant Demographics
The study included prostate cancer patients undergoing radical prostatectomy, with a total of 243 specimens analyzed.
Statistical Information
P-Value
0.0043
Confidence Interval
95% CI 1.6–7.78
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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