Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer
Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer
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DOI：
10.1038/nm1173
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发表时间：
2005-01-01
期刊：
影响因子：
82.9
通讯作者：
Jacks, T
中科院分区：
文献类型：
--
作者：
Dinulescu, DM;Ince, TA;Jacks, T
上皮性卵巢肿瘤由于早期发现困难、缺乏已知的前体病变和高死亡率，在临床、诊断和治疗方面提出了复杂的挑战。子宫内膜样卵巢癌常与子宫内膜异位症相关，但其相关机制尚不清楚。在这里，我们提出了第一个遗传模型的腹膜子宫内膜异位症和卵巢癌样卵巢腺癌的小鼠，都是基于激活的致癌K-ras等位基因。此外，我们发现，表达致癌K-ras或条件性Pten缺失的卵巢表面上皮细胞引起癌前病变的卵巢样腺体形态。此外，卵巢中两种突变的组合导致诱导侵袭性和广泛转移性卵巢癌样腺癌，具有完全转移和仅7周的疾病潜伏期。本研究中描述的卵巢癌模型概括了该人类疾病的特定肿瘤组织形态学和转移潜力。
Epithelial ovarian tumors present a complex clinical, diagnostic and therapeutic challenge because of the difficulty of early detection, lack of known precursor lesions and high mortality rates. Endometrioid ovarian carcinomas are frequently associated with endometriosis, but the mechanism for this association remains unknown. Here we present the first genetic models of peritoneal endometriosis and endometrioid ovarian adenocarcinoma in mice, both based on the activation of an oncogenic K-ras allele. In addition, we find that expression of oncogenic K-ras or conditional Pten deletion within the ovarian surface epithelium gives rise to preneoplastic ovarian lesions with an endometrioid glandular morphology. Furthermore, the combination of the two mutations in the ovary leads to the induction of invasive and widely metastatic endometrioid ovarian adenocarcinomas with complete penetrance and a disease latency of only 7 weeks. The ovarian cancer model described in this study recapitulates the specific tumor histomorphology and metastatic potential of the human disease.