Advances in mouse models of prostate cancer
Advances in mouse models of prostate cancer
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DOI：
10.1017/s1462399408000689
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发表时间：
2008-06-09
影响因子：
6.2
通讯作者：
Leung, Hing Y.
中科院分区：
文献类型：
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作者：
Ahmad, Imran;Sansom, Owen J.;Leung, Hing Y.
科学技术的进步使我们能够操纵小鼠基因组并分析特定遗传变异对体内前列腺癌发展的影响。我们现在可以分析转移性疾病的发生、侵袭和进展的分子基础。目前的小鼠模型使用Cre-loxP技术利用敲除、敲入或表达的条件调节。已被靶向的基因包括同源异型盒基因、肿瘤抑制基因和癌基因、生长因子（及其受体）、类固醇激素和细胞周期调节因子，以及促凋亡蛋白和抗凋亡蛋白。双基因模型表明，从上皮内瘤变（PIN）进展到浸润性癌需要两个“命中”，转移需要两到五个命中。在这里，我们讨论了许多模型，模拟疾病过程的各个方面，如PIN，局部浸润性腺癌和转移性疾病。目前，PB-Cre 4 x PTENloxP/loxP小鼠是跨越从起始到局部侵袭和转移的整个连续体的唯一模型。这种小鼠模型增加了我们对疾病过程的理解，并为新的治疗方法提供了靶点。有希望的是，转基因模型将成为可诱导的，并最终允许时间和空间的基因失活。复合突变模型也将进一步发展，双和三重敲入或敲除系统增加了我们对不同信号级联之间相互作用的了解。
Advances in science and technology have allowed us to manipulate the mouse genome and analyse the effect of specific genetic alterations on the development of prostate cancer in vivo. We can now analyse the molecular basis of initiation, invasion and progression to metastatic disease. The current mouse models utilise knockout, knock-in or conditional regulation of expression using Cre-loxP technology. Genes that have been targeted include homeobox genes, tumour suppressors and oncogenes, growth factors (and their receptors), steroid hormones and cell-cycle regulators, as well as pro- and anti-apoptotic proteins. Bigenic models indicate that that two 'hits' are required for progression from intra-epithelial neoplasia (PIN) to invasion carcinoma, and two to five hits are needed for metastasis. Here, we discuss the numerous models that mimic various aspects of the disease process, such as PIN, locally invasive adenocarcinoma and metastatic disease. Currently the PB-Cre4 x PTENloxP/loxP mouse is the only model that spans the entire continuum from initiation to local invasion and metastasis. Such mouse models increase our understanding of the disease process and provide targets for novel therapeutic approaches. Hopefully, the transgenic models will become inducible and ultimately allow both temporal and spatial gene inactivation. Compound mutational models will also develop further, with double and triple knock-in or knockout systems adding to our knowledge of the interaction between different signalling cascades.