Grabowska Magdalena M, DeGraff David J, Yu Xiuping, Jin Ren Jie, Chen Zhenbang, Borowsky Alexander D, Matusik Robert J
Vanderbilt University, Nashville, TN, USA,
Cancer Metastasis Rev. 2014 Sep;33(2-3):377-97. doi: 10.1007/s10555-013-9487-8.
When the National Institutes of Health Mouse Models of Human Cancer Consortium initiated the Prostate Steering Committee 15 years ago, there were no genetically engineered mouse (GEM) models of prostate cancer (PCa). Today, a PubMed search for "prostate cancer mouse model" yields 3,200 publications and this list continues to grow. The first generation of GEM utilized the newly discovered and characterized probasin promoter driving viral oncogenes such as Simian virus 40 large T antigen to yield the LADY and TRAMP models. As the PCa research field has matured, the second generation of models has incorporated the single and multiple molecular changes observed in human disease, such as loss of PTEN and overexpression of Myc. Application of these models has revealed that mice are particularly resistant to developing invasive PCa, and once they achieve invasive disease, the PCa rarely resembles human disease. Nevertheless, these models and their application have provided vital information on human PCa progression. The aim of this review is to provide a brief primer on mouse and human prostate histology and pathology, provide descriptions of mouse models, as well as attempt to answer the age old question: Which GEM model of PCa is the best for my research question?
15年前,当美国国立卫生研究院人类癌症小鼠模型联盟启动前列腺指导委员会时,还没有前列腺癌(PCa)的基因工程小鼠(GEM)模型。如今,在PubMed上搜索“前列腺癌小鼠模型”能得到3200篇出版物,而且这个列表还在不断增加。第一代GEM利用新发现并表征的前列腺素启动子驱动病毒癌基因,如猿猴病毒40大T抗原,从而产生了LADY和TRAMP模型。随着PCa研究领域的成熟,第二代模型纳入了在人类疾病中观察到的单分子和多分子变化,如PTEN缺失和Myc过表达。这些模型的应用表明,小鼠对发展为侵袭性PCa具有特别的抗性,而且一旦它们患上侵袭性疾病,PCa很少类似于人类疾病。尽管如此,这些模型及其应用为人类PCa进展提供了重要信息。这篇综述的目的是简要介绍小鼠和人类前列腺组织学及病理学,描述小鼠模型,并尝试回答这个由来已久的问题:哪种PCa的GEM模型最适合我的研究问题?