Calcineurin Inhibitor-Induced Overexpression of VEGF in Renal Cancer Cells Involves mTOR through the Regulation of PRAS40
Author Information
Author(s): Basu Aninda, Banerjee Pallavi, Contreras Alan G., Flynn Evelyn, Pal Soumitro
Primary Institution: Children's Hospital, Boston, Massachusetts, United States of America
Hypothesis
CNI treatment and Ras activation promote VEGF overexpression in renal cancer cells through the mTOR pathway.
Conclusion
CNI treatment increases PRAS40 phosphorylation, which activates the mTOR pathway and promotes VEGF overexpression in renal cancer.
Supporting Evidence
- CNI treatment promotes VEGF overexpression in renal cancer cells.
- Rapamycin treatment inhibits CNI-induced VEGF expression.
- Phosphorylation of PRAS40 is critical for mTOR activation.
- Overexpression of PRAS40 reduces CNI- and Ras-induced VEGF transcription.
- CNI treatment increases phospho-PRAS40 levels in renal tumor tissues.
Takeaway
This study shows that a medicine used to prevent organ rejection can also make kidney cancer grow faster by increasing a protein that helps tumors develop.
Methodology
The study involved transfecting renal cancer cells with plasmids and treating them with calcineurin inhibitors and rapamycin, followed by luciferase assays and Western blot analysis.
Potential Biases
Potential bias due to the use of specific cell lines and the focus on particular signaling pathways.
Limitations
The study primarily focuses on in vitro experiments and may not fully represent in vivo conditions.
Participant Demographics
Human renal cancer cell lines (786-0 and Caki-1) were used in the study.
Statistical Information
P-Value
p<0.01
Statistical Significance
p<0.01
Digital Object Identifier (DOI)
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