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Updated: May 16, 2026
08:54
Generation of Tumor Organoids from Genetically Engineered Mouse Models of Prostate Cancer
Published on: June 13, 2019
Sprouty genes function in suppression of prostate tumorigenesis
Jennifer L Schutzman1, Gail R Martin
1Departments of Medicine, University of California, San Francisco, CA 94158, USA.
Summary
Sprouty genes suppress prostate cancer by regulating RAS/ERK and PI3K/AKT pathways. Restoring Sprouty gene expression may prevent high-grade prostatic intraepithelial neoplasia (PIN) and invasive prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Sprouty gene expression is reduced in human prostate cancer, suggesting a tumor suppressor role.
- Prostate tumorigenesis involves complex genetic interactions and signaling pathway dysregulation.
Purpose of the Study:
- To investigate the role of Sprouty genes (Spry1 and Spry2) in mouse prostate tumor suppression.
- To elucidate the genetic interactions between Sprouty genes and the Pten tumor suppressor gene.
- To determine the impact of Sprouty genes on RAS/ERK and PI3K/AKT signaling pathways in prostate cancer.
Main Methods:
- Inactivation of Spry1 and Spry2 in mouse prostate epithelium.
- Utilizing Pten heterozygous null mice.
- Introducing Spry2 gain-of-function transgenes.
- Analysis of signaling pathway activation (RAS/ERK1/2 and PI3K/AKT).
Main Results:
- Loss of Spry1 and Spry2 causes hyperplasia and low-grade prostatic intraepithelial neoplasia (PIN).
- Combined loss of Spry1/Spry2 and Pten heterozygosity accelerates PIN and invasion.
- Spry2 gain-of-function suppresses tumorigenesis in Pten-deficient prostates.
- Sprouty gene loss leads to hyperactive RAS/ERK1/2 and cooperates with Pten loss to promote PI3K/AKT signaling.
Conclusions:
- Sprouty genes (Spry1, Spry2) are critical suppressors of prostate tumorigenesis in mice.
- A key genetic interaction exists between Sprouty genes and Pten in prostate cancer development.
- Restoring Sprouty gene expression may offer a therapeutic strategy against high-grade PIN and invasive prostate cancer.
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