Genetically defined mouse models that mimic natural aspects of human prostate cancer development.

Abstract

This review is focused on mouse models for prostate cancer that have been designed on the basis of genetic alterations that are frequently found in human prostate cancer. It begins with an analysis of the similarities and differences in the gross and microscopic anatomy of the mouse and human prostate glands, and extends to the pathologies induced in the genetically manipulated mouse prostate in comparison with the sporadic development of the disease in humans. Major achievements have been made in modeling human prostate cancer in mice in recent years. There are models which display slow, temporal development of increasingly severe preneoplastic lesions, which are remarkably restricted to the prostate gland, a property similar to the aging-related progression of these lesions in humans. Other models rapidly progress to local invasive adenocarcinoma, and, in some of them metastasis is manifested subsequently with defined kinetics. Global assessment of molecular changes in the prostate of the genetically manipulated mice is increasingly underscoring the validity of the models through identification of 'signature' genes which are associated with the organ-confined primary or distant metastases of human prostate cancer. Taken together, various 'natural' models depicting stages of the disease, ranging from the early preneoplastic lesions to metastatic prostate cancer, now provide new tools both for exploring the molecular mechanism underlying prostate cancer and for development or testing of new targeted therapies.

Androgen receptor targets NFκB and TSP1 to suppress prostate tumor growth in vivo

“…The differences in structure, physiology and cancer progression in mouse and human prostate 59 make it essential to complement the findings from genetically altered mice with those from xenografted tumors. Indeed, stroma and the smooth muscle are major structural and functional components in human, but not in mouse prostate.…”

“…Lobular structure is seen in the mouse but not in human prostate, while mice have no transitional zone, prostatic urethra and capsule. 59 Most importantly, prostate cancer does not occur spontaneously in wild-type mice; the major- ity of mouse models are driven by SV-40 large and small T viral oncogenes. Other suspect oncogenes and tumor suppressors yield intraepithelial neoplasia (PIN) but not PrCa.…”

Anti-inflammatory therapies in TRAMP mice: delay in PCa progression

“…Thus, the percentage of each lesion for each experimental group was established. The morphological classification of different degrees of prostatic lesions in TRAMP mice was partially based on descriptions made by Roy-Burman et al (2004). The presence of undifferentiated adenocarcinoma was calculated considering the total number of 22-weekold mice (Fig.…”

Dissociation of Epithelial and Neuroendocrine Carcinoma Lineages in the Transgenic Adenocarcinoma of Mouse Prostate Model of Prostate Cancer

“…1,2 Numerous experimental systems have been developed to study the genetic and biological aspects of prostate cancer development including cell culture systems, xenografts, and genetically engineered mouse models. [3][4][5][6][7][8][9][10] Animal models that faithfully recapitulate the stages of human cancer progression are valuable but rare. In comparison to cell culture, mouse models are advantageous because they offer a system in which all aspects of disease progression can be studied in a setting where both genetic background and environment can be controlled.…”