PROSTATE AND MAMMARY ADENOCARCINOMA IN TRANSGENIC MICE CARRYING A RAT C3(1) SIMIAN-VIRUS-40 LARGE TUMOR-ANTIGEN FUSION GENE
PROSTATE AND MAMMARY ADENOCARCINOMA IN TRANSGENIC MICE CARRYING A RAT C3(1) SIMIAN-VIRUS-40 LARGE TUMOR-ANTIGEN FUSION GENE
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DOI：
10.1073/pnas.91.23.11236
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发表时间：
1994-11-08
影响因子：
11.1
通讯作者：
GREEN, JE
中科院分区：
文献类型：
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作者：
MAROULAKOU, IG;ANVER, M;GREEN, JE
在大鼠前列腺类固醇结合蛋白[C3(1)]基因的调控下，建立了表达猴病毒40早期区域转化序列的重组基因，建立了前列腺癌和乳腺癌的转基因小鼠模型。雄性转基因小鼠在生命早期出现前列腺增生，在大多数动物中发展为腺瘤或腺癌，存活到7个月以上。已观察到前列腺癌转移到肺。相同母系的雌性动物一般在3个月龄时发生乳腺增生，随后在6个月龄时100%发展为乳房腺癌。Northern印迹和免疫组织化学分析表明，肿瘤的发生与转基因的表达有关。这些实验的结果表明，这些实验中使用的C3(1)调节区对于前列腺和乳腺的靶向表达是有用的。据我们所知，这个实验系统是第一个报道的前列腺癌转基因小鼠模型。这些转基因动物提供了研究体内激素反应元件以及从正常组织到前列腺癌和乳腺癌的多阶段进展的机会。
A transgenic mouse model for prostate and mammary cancer has been developed in mice containing a recombinant gene expressing the simian virus 40 early-region transforming sequences under the regulatory control of the rat prostatic steroid binding protein [C3(1)] gene. Male transgenic mice develop prostatic hyperplasia in early life that progresses to adenoma or adenocarcinoma in most animals surviving to longer than 7 months of age. Prostate cancer metastases to lung have been observed. female animals from the same founder lines generally develop mammary hyperplasia by 3 months of age with subsequent development of mammary adenocarcinoma by 6 months of age in 100% of the animals. The development of tumors correlates with the expression of the transgene as determined by Northern blot and immunohistochemical analyses. The results of these experiments demonstrate that the C3(1) regulatory region used in these experiments is useful for targeting expression to the prostate and mammary gland. To our knowledge, this experimental system is the first reported transgenic mouse model for prostate cancer. These transgenic animals offer the opportunity to study hormone response elements in vivo and the multistage progression from normal tissue to carcinoma in the prostate and mammary glands.