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Identification, Histological Characterization, and Dissection of Mouse Prostate Lobes for In Vitro 3D Spheroid Culture Models
Published on: September 18, 2018
Mapping prostate cancer pathobiology: A review of genetically engineered mouse models (GEMMs)
Filippo Pederzoli1, Hubert Pakula1, Silvia Rodrigues1
1Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA.
Abstract:
Prostate cancer (PCa) is the second most common malignancy in men and represents about 7% of newly diagnosed tumors worldwide (and up to 15% in developed countries). At the genomic level, PCa is generally characterized by copy number alterations and/or gene structural rearrangements that encompass multiple genes, including oncogenes such as ERG and MYC and tumor suppressor genes such as TP53 and PTEN. To advance our understanding of the role of specific genomic alterations in PCa, genetically engineered mouse models (GEMMs) have been pivotal in complementing large-scale human sequencing initiatives. In this Review, we focus on the main altered genes in PCa and how they have been modeled in different GEMMs to study the molecular mechanisms underlying PCa tumorigenesis and progression.
Insights
Prostate cancer (PCa) is a common male malignancy. This review details key gene alterations in PCa and their modeling in genetically engineered mouse models (GEMMs) to understand tumorigenesis.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Prostate cancer (PCa) is the second most common cancer in men globally.
- Genomic alterations, including copy number changes and gene rearrangements (e.g., ERG, MYC, TP53, PTEN), are hallmarks of PCa.
- Understanding these alterations is crucial for advancing PCa research.
Purpose of the Study:
- To review the primary genes altered in prostate cancer.
- To discuss how genetically engineered mouse models (GEMMs) represent these key genomic alterations.
- To explore the utility of GEMMs in studying PCa molecular mechanisms.
Main Methods:
- Review of existing literature on PCa genomics.
- Analysis of genetically engineered mouse models (GEMMs) relevant to PCa.
- Focus on modeling key oncogenes and tumor suppressor genes.
Main Results:
- Identification of frequently altered genes in PCa, including oncogenes (ERG, MYC) and tumor suppressor genes (TP53, PTEN).
- Demonstration of various GEMMs that recapitulate specific genomic alterations found in human PCa.
- Highlighting the role of GEMMs in dissecting molecular pathways of PCa development.
Conclusions:
- Genetically engineered mouse models are essential tools for studying prostate cancer genomics.
- GEMMs facilitate the investigation of molecular mechanisms driving PCa initiation and progression.
- This review synthesizes current knowledge on PCa-associated gene alterations and their modeling.
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