Induction of ovarian cancer by defined multiple genetic changes in a mouse model system
Induction of ovarian cancer by defined multiple genetic changes in a mouse model system
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DOI：
10.1016/s1535-6108(01)00002-2
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发表时间：
2002-02-01
期刊：
影响因子：
50.3
通讯作者：
Varmus, HE
中科院分区：
文献类型：
--
作者：
Orsulic, S;Li, Y;Varmus, HE
我们利用禽逆转录病毒基因传递技术，将多个基因导入成年小鼠卵巢体细胞，建立了卵巢癌小鼠模型。用携带癌基因和标记基因编码序列的多个载体在体外有效感染了表达禽TVA受体编码基因的转基因小鼠卵巢细胞。当目标细胞来源于缺乏p53的TVA转基因小鼠时，在皮下、腹腔或卵巢部位注射感染细胞时，添加任意两个致癌基因c-myc、K-ras和Akt都足以诱导卵巢肿瘤形成。我们证明卵巢表面上皮是这些卵巢癌的前体组织，癌基因的引入导致卵巢表面上皮细胞的表型改变。小鼠卵巢肿瘤的快速进展和腹腔内转移扩散与人卵巢癌相似。
We have developed a mouse model for ovarian carcinoma by using an avian retroviral gene delivery technique for the introduction of multiple genes into somatic ovarian cells of adult mice. Ovarian cells from transgenic mice engineered to express the gene encoding the avian receptor TVA were efficiently infected in vitro with multiple vectors carrying coding sequences for oncogenes and marker genes. When target cells were derived from TVA transgenic mice deficient for p53, the addition of any two of the oncogenes c-myc, K-ras, and Akt were sufficient to induce ovarian tumor formation when infected cells were injected at subcutaneous, intraperitoneal, or ovarian sites. We demonstrated that the ovarian surface epithelium is the precursor tissue for these ovarian carcinomas, and that introduction of oncogenes causes phenotypic changes in the ovarian surface epithelial cells. The induced ovarian tumors in mice resembled human ovarian carcinomas in their rapid progression and intraperitoneal metastatic spread.