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Updated: Jul 11, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
PI3K/PTEN/AKT signaling regulates prostate tumor angiogenesis
Jing Fang1, Min Ding, Lily Yang
1Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506-9300, USA.
Abstract:
PI3K pathway exerts its function through its downstream molecule AKT in regulating various cell functions including cell proliferation, cell transformation, cell apoptosis, tumor growth and angiogenesis. PTEN is an inhibitor of PI3K, and its loss or mutation is common in human prostate cancer. But the direct role and mechanism of PI3K/PTEN signaling in regulating angiogenesis and tumor growth in vivo remain to be elucidated. In this study, by using chicken chorioallantoic membrane (CAM) and in nude mice models, we demonstrated that inhibition of PI3K activity by LY294002 decreased PC-3 cells-induced angiogenesis. Reconstitution of PTEN, the molecular inhibitor of PI3K in PC-3 cells inhibited angiogenesis and tumor growth. Immunohistochemical staining indicated that PTEN expression suppressed HIF-1alpha, VEGF and PCNA expression in the tumor xenographs. Similarly, expression of AKT dominant negative mutant also inhibited angiogenesis and tumor growth, and decreased the expression of HIF-1alpha and VEGF in the tumor xenographs. These results suggest that inhibition of PI3K signaling pathway by PTEN inhibits tumor angiogenesis and tumor growth. In addition, we found that AKT is the downstream target of PI3K in controlling angiogenesis and tumor growth, and PTEN could inhibit angiogenesis by regulating the expression of HIF-1 and VEGF expression through AKT activation in PC-3 cells.
Insights
The Phosphatidylinositol 3-kinase (PI3K) pathway drives tumor growth and angiogenesis. PTEN, a PI3K inhibitor, suppresses these processes by downregulating AKT, HIF-1alpha, and VEGF, offering therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The PI3K/AKT pathway regulates cell proliferation, apoptosis, and angiogenesis.
- PTEN is a key inhibitor of PI3K, and its loss is frequent in prostate cancer.
- The precise role of PI3K/PTEN signaling in tumor growth and angiogenesis requires further investigation.
Purpose of the Study:
- To elucidate the mechanism by which PI3K/PTEN signaling regulates angiogenesis and tumor growth in vivo.
- To investigate the role of PTEN in suppressing prostate cancer progression.
Main Methods:
- Utilized chicken chorioallantoic membrane (CAM) and nude mouse models.
- Inhibited PI3K activity with LY294002 and reconstituted PTEN in PC-3 cells.
- Assessed angiogenesis and tumor growth, and performed immunohistochemical staining for HIF-1alpha, VEGF, and PCNA.
Main Results:
- PI3K inhibition by LY294002 reduced angiogenesis induced by PC-3 cells.
- PTEN reconstitution in PC-3 cells suppressed angiogenesis and tumor growth.
- PTEN and AKT inhibition decreased expression of HIF-1alpha and VEGF, key regulators of angiogenesis.
Conclusions:
- PTEN inhibits tumor angiogenesis and growth by suppressing the PI3K/AKT signaling pathway.
- AKT acts as a downstream mediator of PI3K in controlling angiogenesis and tumor growth.
- PTEN's anti-angiogenic effect is mediated through the AKT pathway, impacting HIF-1 and VEGF expression.
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