PROSTATE-CANCER IN A TRANSGENIC MOUSE
PROSTATE-CANCER IN A TRANSGENIC MOUSE
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DOI：
10.1073/pnas.92.8.3439
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发表时间：
1995-04-11
影响因子：
11.1
通讯作者：
ROSEN, JM
中科院分区：
文献类型：
--
作者：
GREENBERG, NM;DEMAYO, F;ROSEN, JM
了解前列腺癌的生物学进展缓慢，因为很少有动物研究模型可用于研究这种独特的人类疾病的频谱。为了建立前列腺癌的动物模型，利用前列腺特异性大鼠前盆地启动子驱动猴病毒40大肿瘤抗原编码区表达，制备了多株转基因小鼠。表达高水平转基因的小鼠表现出与人类前列腺癌相似的进行性前列腺疾病，从轻度上皮内增生到大的多结节恶性肿瘤。早在10周大的时候就能在前列腺中检测到前列腺肿瘤。肿瘤组织的免疫组织化学分析表明，背外侧前列腺特异性分泌蛋白局限于低分化肿瘤肿块附近或内部的高分化导管上皮细胞。在晚期人类前列腺癌中观察到，小鼠前列腺肿瘤也显示出核p53水平升高和雄激素受体异质表达模式减少。可再生发生前列腺癌的转基因小鼠育种系的建立，为研究正常前列腺细胞转化的分子基础及转移性前列腺癌进展的影响因素提供了动物模型体系。
Progress toward understanding the biology of prostate cancer has been slow due to the few animal research models available to study the spectrum of this uniquely human disease. To develop an animal model for prostate cancer, several lines of transgenic mice were generated by using the prostate-specific rat probasin promoter to drive expression of the simian virus 40 large tumor antigen-coding region. Mice expressing high levels of the transgene display progressive forms of prostatic disease that histologically resemble human prostate cancer, ranging from mild intraepithelial hyperplasia to large multinodular malignant neoplasia. Prostate tumors have been detected specifically in the prostate as early as 10 weeks of age. Immunohistochemical analysis of tumor tissue has demonstrated that dorsolateral prostate-specific secretory proteins were confined to well-differentiated ductal epithelial cells adjacent to, or within, the poorly differentiated tumor mass. Prostate tumors in the mice also display elevated levels of nuclear p53 and a decreased heterogeneous pattern of androgen-receptor expression, as observed in advanced human prostate cancer. The establishment of breeding lines of transgenic mice that reproducibly develop prostate cancer provides an animal model system to study the molecular basis of transformation of normal prostatic cells and the factors influencing the progression to metastatic prostate cancer.