Mouse Models For Human Prostate Cancer: Xenograft Vs Genetically Engineered Mouse Model

Abstract

Prostate cancer is among the commonest cancers in men with high mortality. It is thought to arise from accumulated genetic mutations that may transform benign prostatic epithelium to prostatic intraepithelial neoplasia (PIN). With additional genetic alterations, PIN progresses to invasive cancer, and finally to metastatic disease. Metastatic prostate cancer is generally accompanied by emergence of androgen-independent cancer. About 70% of primary prostate cancers exhibit a loss of at least one PTEN allele and loss of both alleles is associated with advanced disease. PTEN is tumor suppressor gene that works by suppressing the activity of Akt /PKB pathway. Over expression of many oncogenes has also been observed in many human prostate cancers. Animal models are crucial to understand the underlying biology and to test novel prevention and treatment strategies for prostate cancer. Appropriate animal models should recapitulate genetic alterations and clinical courses of human prostate cancer.

The following paper describes important characteristics of genetically modified mouse model and xenograft mouse model. We performed recent literature search for human prostate cancer mouse models.

Numerous mouse models of human prostate cancer have been generated and exhibit common characteristics of human prostate cancer.  Initially, the immunocompromised mouse was used as a xenograft model for in vivo analyses of human prostate cell lines. This approach does not however consider the heterogonous nature of prostate cancer as a disease with complex interactions between the transformed cells, the resident cells, the stromal cells, the endothelial cells and the immune cells all which participate in the disease pathogenesis. One of the genetically engineered mouse models is the prostate specific Cre-mediated conditional expression of Myc oncogene by removal of a conditional STOP sequence (PB-c-Myc,).This model progresses to invasive carcinoma without metastasis. The other is a conditional PTEN Knockout model using Cre recombinase targeted to the prostate specific probasin promoter. This model recapitulates the human prostate cancer to metastasis carcinoma.

Genetically engineered mouse models are more able to recapitulate the human prostate cancer compare to the xenograft. The PTEN knock out mouse is suitable for understanding molecular basis of the disease. Xenograft will remain more useful testing of therapy. In the future more sophisticated prostate animal model should be available so as to recapitulate the heterogeneity of the disease

Keywords: Knockout, Mouse model, Oncogene, prostate cancer, Xenograft