Winter S F, Cooper A B, Greenberg N M
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Prostate Cancer Prostatic Dis. 2003;6(3):204-11. doi: 10.1038/sj.pcan.4500655.
Transgenic mouse models are proving to be invaluable in our effort to understand the molecular basis of metastatic prostate cancer (CaP). We review and discuss how current animal models have contributed to our understanding of the metastatic cascade and how transgenic technology is being used to develop the next generation of mouse models. Our goal is to provide a review of the recent advances and provide a framework for further studies.
We performed a MEDLINE search of the literature on CaP metastasis transgenic and animal models.
We present a summary of the characteristics of nine different animal models of CaP. Each model is unique and provides valuable insight into the molecular mechanisms governing the progression of CaP. Our experience with transgenic models and all the new data from the literature predicts that we will be able to develop genetically engineered mice that accurately mimic the heterogeneity, androgen-independent growth, and metastatic spread seen in clinical disease.
In order to elucidate the molecular mechanisms of CaP metastasis, it will be necessary to compare gene and protein expression patterns and biochemical analyses of clinical metastatic disease with data obtained from current models. We will also need to refine our ability to engineer and characterize genetic perturbation models. This type of integrative and iterative approach should facilitate better understanding of the molecular biology of CaP metastases.
转基因小鼠模型在我们理解转移性前列腺癌(CaP)分子基础的努力中已被证明具有极高价值。我们回顾并讨论当前动物模型如何有助于我们理解转移级联反应,以及转基因技术如何被用于开发下一代小鼠模型。我们的目标是对近期进展进行综述,并为进一步研究提供一个框架。
我们对关于CaP转移、转基因和动物模型的文献进行了MEDLINE检索。
我们总结了九种不同CaP动物模型的特征。每种模型都独一无二,为控制CaP进展的分子机制提供了有价值的见解。我们在转基因模型方面的经验以及文献中的所有新数据预测,我们将能够开发出准确模拟临床疾病中所见异质性、雄激素非依赖性生长和转移扩散的基因工程小鼠。
为了阐明CaP转移的分子机制,有必要将临床转移性疾病的基因和蛋白质表达模式及生化分析与从当前模型获得的数据进行比较。我们还需要提高构建和表征基因扰动模型的能力。这种整合和迭代的方法应有助于更好地理解CaP转移的分子生物学。