Powell W C, Cardiff R D, Cohen M B, Miller G J, Roy-Burman P
Dept. of Pathology, Keck School of Medicine at USC, Los Angeles, CA 90033, USA.
Curr Drug Targets. 2003 Apr;4(3):263-79. doi: 10.2174/1389450033491145.
Animal models of prostate cancer have been limited in number and in relevance to the human disease. With the advancement of transgenic and knockout technologies, combined with tissue specific promoters and tissue-specific gene ablation, a new generation of mouse models has emerged. This review will discuss various animal models and their inherent strengths and weaknesses. A primary emphasis is placed on mouse models that have been designed on the basis of genetic alterations that are frequently found in human prostate cancer. These models display slow, temporal development of increasingly severe histopathologic lesions, which are remarkably restricted to the prostate gland, a property similar to the ageing related progression of this disease in humans. The preneoplastic lesions, akin to what is considered as prostatic intraepithelial neoplasia, are consistent major phenotypes in the models, and, therefore. are discussed for histopathologic criteria that may distinguish their progressions or grades. Finally, considering that prostate cancer is a complex multifocal disease, which is likely to require multiple genetic/epigenetic alterations, many of these models have already been intercrossed to derive mice with compound genetic alterations. It is predicted that these and subsequent compound mutant mice should represent "natural" animal models for investigating the mechanism of development of human prostate diseases, as well as, for preclinical models for testing therapeutics.
前列腺癌的动物模型在数量上以及与人类疾病的相关性方面都存在局限。随着转基因和基因敲除技术的进步，结合组织特异性启动子和组织特异性基因消融技术，新一代小鼠模型应运而生。本综述将讨论各种动物模型及其固有的优缺点。主要重点是基于人类前列腺癌中常见的基因改变而设计的小鼠模型。这些模型呈现出日益严重的组织病理学病变的缓慢、渐进性发展，且显著局限于前列腺，这一特性类似于人类前列腺癌与衰老相关的进展情况。类似于前列腺上皮内瘤变的癌前病变是这些模型中一致的主要表型，因此，将讨论可能区分其进展或分级的组织病理学标准。最后，鉴于前列腺癌是一种复杂的多灶性疾病，可能需要多种基因/表观遗传改变，许多此类模型已经进行了杂交以获得具有复合基因改变的小鼠。预计这些以及后续的复合突变小鼠应代表用于研究人类前列腺疾病发生机制的“天然”动物模型，以及用于测试治疗方法的临床前模型。
