Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium.
Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium.
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发表时间：
2003-07
期刊：
影响因子：
11.2
通讯作者：
A. Flesken-Nikitin;Kyung-Chul Choi;J. P. Eng;Elena N. Shmidt;A. Nikitin
中科院分区：
文献类型：
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作者：
A. Flesken-Nikitin;Kyung-Chul Choi;J. P. Eng;Elena N. Shmidt;A. Nikitin
p53和Rb信号通路在上皮性卵巢癌（epithelial ovarian cancer，EOC）中的改变是常见的，但其在EOC发生中的作用尚不清楚。使用一个单一的囊内管理的重组腺病毒表达Cre，我们证明，同时失活的p53和Rb 1是足够的条件基因等位基因纯合子小鼠卵巢上皮癌的可重复诱导。与女性疾病进展相似，卵巢肿瘤通过腹膜内扩散，形成腹水并转移到对侧卵巢、肺和肝。这些结果建立了EOC发病机制中p53和Rb 1通路之间的关键相互作用，并提供了散发性EOC的遗传定义的免疫活性小鼠模型。
Alterations in p53 and Rb pathways are observed frequently in epithelial ovarian cancer (EOC).However, their roles in EOC initiation remain uncertain. Using a single intrabursal administration of recombinant adenovirus expressing Cre, we demonstrate that concurrent inactivation of p53 and Rb1 is sufficient for reproducible induction of ovarian epithelial carcinogenesis in mice homozygous for conditional gene alleles. Similarly to progression of disease in women, ovarian neoplasms spread i.p., forming ascites, and metastasize to the contralateral ovary, the lung, and the liver. These results establish critical interactions between p53 and Rb1 pathways in EOC pathogenesis, and provide a genetically defined immunocompetent mouse model of sporadic EOC.