Pathologic progression of autochthonous prostate cancer in the TRAMP model
Pathologic progression of autochthonous prostate cancer in the TRAMP model
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DOI：
10.1038/sj/pcan/4500296
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发表时间：
1999-03-01
影响因子：
4.8
通讯作者：
Greenberg, NM
中科院分区：
文献类型：
--
作者：
Gingrich, JR;Barrios, RJ;Greenberg, NM
利用转基因技术在特定时间在特定细胞类型中操纵基因表达的能力已经允许开发可以模拟人类疾病的新型小鼠模型系统。我们以前建立了转基因小鼠前列腺癌（TRAMP）前列腺癌模型，使用大鼠probasin启动子直接表达的SV40早期基因的前列腺上皮。雄性TRAMP小鼠表现出一致的前列腺特异性表达模式，并发生前列腺上皮内瘤变，其将变得具有侵袭性并主要转移到淋巴结和肺。在本文中，我们报告了我们继续使用该模型的经验，并提出了一个标准化的组织学分级系统，以指定低级别和高级别的前列腺上皮内瘤和高，中，低分化的前列腺腺癌。此外，我们还证实了雄激素受体表达在病理进展过程中的持续性，并描述了局部和转移性前列腺癌中细胞角蛋白表达的异质性。最后，我们报告了我们的观察，肿瘤的表型变异性和病理进展的TRAMP发生作为一个功能的遗传背景。
The ability to manipulate gene expression in specific cell types at specific times utilizing transgenic technology has allowed the development of novel mouse model systems that can mimic human disease. We have previously established the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model for prostate cancer using the rat probasin promoter to direct expression of the SV40 early genes to prostate epithelium. Male TRAMP mice exhibit consistent prostate-specific patterns of expression and develop prostatic intraepithelial neoplasia that will become invasive and metastasize primarily to the lymph nodes and lungs. In this paper we report our continued experience with this model and present a standardized histologic grading system to designate low and high grade prostatic intraepithelial neoplasia and well, moderate, and poorly differentiated prostate adenocarcinoma. In addition, we demonstrate the persistence of androgen receptor expression during pathologic progression and characterize heterogeneous cytokeratin expression in localized and metastatic prostate cancer. Finally, we report on our observations that phenotypic variability in tumor and pathologic progression in TRAMP occurs as a function of genetic background.