Departments of Urology, Medicine, Systems Biology, and Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York 10032.
Cold Spring Harb Perspect Med. 2019 Feb 1;9(2):a030528. doi: 10.1101/cshperspect.a030528.
Recent genomic sequencing analyses have unveiled the spectrum of genomic alterations that occur in primary and advanced prostate cancer, raising the question of whether the corresponding genes are functionally relevant for prostate tumorigenesis, and whether such functions are associated with particular disease stages. In this review, we describe genetically engineered mouse models (GEMMs) of prostate cancer, focusing on those that model genomic alterations known to occur in human prostate cancer. We consider whether the phenotypes of GEMMs based on gain or loss of function of the relevant genes provide reliable counterparts to study the predicted consequences of the corresponding genomic alterations as occur in human prostate cancer, and we discuss exceptions in which the GEMMs do not fully emulate the expected phenotypes. Last, we highlight future directions for the generation of new GEMMs of prostate cancer and consider how we can use GEMMs most effectively to decipher the biological and molecular mechanisms of disease progression, as well as to tackle clinically relevant questions.
最近的基因组测序分析揭示了原发性和晚期前列腺癌中发生的基因组改变谱，提出了以下问题：相应的基因是否对前列腺肿瘤发生具有功能相关性，以及这些功能是否与特定的疾病阶段相关。在这篇综述中，我们描述了前列腺癌的基因工程小鼠模型（GEMM），重点介绍了那些模拟已知在人类前列腺癌中发生的基因组改变的模型。我们考虑了基于相关基因的功能获得或缺失的 GEMM 表型是否为研究相应的基因组改变在人类前列腺癌中发生的预期后果提供了可靠的对应物，并且我们讨论了在哪些情况下 GEMM 不能完全模拟预期表型的情况。最后，我们强调了生成新的前列腺癌 GEMM 的未来方向，并考虑了如何最有效地利用 GEMM 来破译疾病进展的生物学和分子机制，以及解决临床相关问题。
