Genetically Engineered Mice Model Prostate Cancer Development

Researchers at Vanderbilt University have developed a genetically engineered mouse model that captures the essence of invasive prostate cancer. The mouse model, which utilizes the probasin (PB) and prostate-specific antigen (PSA) promoters, has been used to study the molecular basis of prostate cancer development, progression, and metastasis. The model has been shown to represent the entire continuum of prostate adenocarcinoma development, tumor progression, and metastasis.

Key Takeaways:

• Genetically engineered mouse models have been generated to study the molecular basis of prostate cancer development, progression, and metastasis.
• The probasin (PB) and prostate-specific antigen (PSA) promoters are critical for generating sufficient levels of transgene expression to elicit a phenotypic response.
• Target genes have included growth factors, cell cycle regulators, pro- and antiapoptotic proteins, steroid hormone and growth factor receptors, oncogenes, tumor suppressors, and homeobox genes.
• The experimental approaches used to generate these mouse models include overexpression of the transgene, knock-out/knock-in of transgene expression, and conditional regulation of expression using Cre/lox technology.
• The PB-Cre4 x PTENloxp/loxp model represents the entire continuum of prostate adenocarcinoma development, tumor progression, and metastasis.
• Analysis of bigenic mouse models indicates that two genetic events are generally required for progression from high-grade intraepithelial neoplasia (HGPIN) to locally invasive adenocarcinoma, and that two to five genetic events can promote metastasis to distant sites.
• Studying the effects of genetic perturbation on prostate cancer biology will increase our understanding of the disease process and potentially provide targets for developing novel therapeutic approaches.

Statistics:

• Two genetic events are generally required for progression from high-grade intraepithelial neoplasia (HGPIN) to locally invasive adenocarcinoma.
• Two to five genetic events can promote metastasis to distant sites.
• The PB-Cre4 x PTENloxp/loxp model represents the entire continuum of prostate adenocarcinoma development, tumor progression, and metastasis.

Sources:

• Kasper, S., et al. (2005). Survey of genetically engineered mouse models for prostate cancer: Analyzing the molecular basis of prostate cancer development, progression, and metastasis. Journal of Cellular Biochemistry, 94(2), 279-297.
• Vanderbilt University, Center for Medicine, A-1302 MCN, 1161 21st Avenue S, Nashville, TN 37232, USA.
• Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.