Deciphering Cancer Complexities in Genetically Engineered Mice
Open accessAbstract
Because the pRb pathway is disrupted in most solid human cancers, we have generated genetically engineered mouse cancer models by inactivating pRb function in several cell types, including astrocytes and mammary, prostate, ovarian, and brain choroid plexus epithelia. In every case, proliferation and apoptosis are acutely induced, predisposing to malignancy. Cell type dictates the pathways involved in tumor progression. In the astrocytoma model, we developed strategies to induce events in the adult brain, either throughout the tissue or focally. Both K-Ras activation and Pten inactivation play significant roles in progression. In the prostate model, adenocarcinoma progression depends on Pten inactivation. However, nonautonomous induction of p53 in the mesenchyme leads to evolution of both compartments, with p53 loss occurring in the mesenchyme. Thus, studies in these models continue to identify key tumorigenesis mechanisms. Furthermore, we are hopeful that the models will provide useful preclinical systems for diagnostic and therapeutic development.
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Different cell types respond differently to loss of Rb family members.
“These experiments illustrate the point that different cell types respond differently to loss of Rb family members, which could dictate the requirement for specific mutations during tumour progression161.”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [161]
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Cellular mechanisms of tumour suppression by the retinoblastoma gene
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- Authors
- SIMIN, K., HILL, R., SONG, Y., ZHANG, Q., BASH, R., CARDIFF, R. D., YIN, C., XIAO, A., McCARTHY, K., & DYKE, T. V.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of California, Los Angeles (US)
- University of California, Davis (US)
- Rockefeller University (US)
- Venue
- Cold Spring Harbor Symposia on Quantitative Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-01-01
- Volume
- 70
- Issue
- 0
- Pages
- 283-290
- ISSN
- 0091-7451 (ISSN-L)
- 1943-4456
- OpenAlex
- W1976720800
- Cited by
- 8
- References
- 23
- Citations by year
- 2013: 1 · 2012: 2
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Symposia on Quantitative Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- Goldhirsh Foundation
- Massachusetts Institute of Technology
- University of Pittsburgh
- National Cancer Institute (U01CA084294, U01CA84294, R01-CA46283, R01CA046283, U01 CA84314, U01CA084314)
- Fogarty International Center
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- pRb pathway, genetically engineered mouse models, tumor progression, astrocytoma, prostate adenocarcinoma, ovarian cancer, choroid plexus epithelium, mammary tumors, KRAS activation, PTEN inactivation, p53 deficiency, apoptosis, cell proliferation
- MeSH terms
- Animals, Astrocytoma, Female, Genetic Engineering, Genetic Vectors, Humans, Male, Mice, Transgenic, Neoplasms, Experimental, Prostatic Neoplasms, Genes, ras, Retinoblastoma Protein, Genes, Retinoblastoma, Mice, Knockout, PTEN Phosphohydrolase, Mice
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