通过PTEN/AKT通路对人类前列腺癌进行临床前重塑
Preclinical Remodeling of Human Prostate Cancer through the PTEN/AKT Pathway.
作者信息
De Velasco Marco A, Uemura Hirotsugu
机构信息
Department of Urology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
出版信息
Adv Urol. 2012;2012:419348. doi: 10.1155/2012/419348. Epub 2012 Feb 21.
Abstract
Knowledge gained from the identification of genetic and epigenetic alterations that contribute to the progression of prostate cancer in humans is now being implemented in the development of functionally relevant translational models. GEM (genetically modified mouse) models are being developed to incorporate the same molecular defects associated with human prostate cancer. Haploinsufficiency is common in prostate cancer and homozygous loss of PTEN is strongly correlated with advanced disease. In this paper, we discuss the evolution of the PTEN knockout mouse and the cooperation between PTEN and other genetic alterations in tumor development and progression. Additionally, we will outline key points that make these models key players in the development of personalized medicine, as potential tools for target and biomarker development and validation as well as models for drug discovery.
摘要
从鉴定导致人类前列腺癌进展的基因和表观遗传改变中获得的知识，目前正应用于功能相关的转化模型的开发。正在开发基因工程小鼠（GEM）模型，以纳入与人类前列腺癌相关的相同分子缺陷。单倍体不足在前列腺癌中很常见，PTEN的纯合缺失与晚期疾病密切相关。在本文中，我们讨论了PTEN基因敲除小鼠的演变以及PTEN与其他基因改变在肿瘤发生和进展中的协同作用。此外，我们将概述使这些模型成为个性化医疗发展的关键因素，作为靶点和生物标志物开发与验证的潜在工具以及药物发现的模型。
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