HEREDITARY RENAL-CELL CARCINOMA IN THE EKER RAT - A RODENT FAMILIAL CANCER SYNDROME
HEREDITARY RENAL-CELL CARCINOMA IN THE EKER RAT - A RODENT FAMILIAL CANCER SYNDROME
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DOI：
10.1016/s0022-5347(17)37087-8
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发表时间：
1992-12-01
影响因子：
6.6
通讯作者：
WALKER, CL
中科院分区：
文献类型：
--
作者：
EVERITT, JI;GOLDSWORTHY, TL;WALKER, CL
描述了一种遗传性癌症的啮齿动物模型，其中单个基因突变使大鼠易患双侧多中心肾细胞癌（RCC）。这种大鼠遗传性癌症综合征与von Hippel-Lindau病（VHLD）有某些相似之处。除了早期发生与人RCC形态相似的肾上皮肿瘤外，携带RCC基因的大鼠在以后的生活中易发生继发性原发癌。脾血管增生性病变，包括血管肉瘤，见于23%的14个月大的大鼠，两种性别的肾肿瘤。在14个月大时，62%的肾细胞肿瘤雌性大鼠出现下生殖道肉瘤，可能起源于平滑肌。受影响动物的非携带者兄弟姐妹没有肾脏、生殖系统或脾脏肿瘤。在这种大鼠常染色体显性遗传病中发现一种特殊的家族性肿瘤，包括多中心性双侧肾细胞癌，表明这种综合征类似于人类VHLD。除了它的有用性研究的生化和分子机制的肾脏致癌作用，这种动物模型将提供一个独特的工具来研究癌症易感基因如何与环境风险因素，如化学致癌物相互作用。
A rodent model of hereditary cancer in which a single gene mutation predisposes rats to bilateral multicentric renal cell carcinoma (RCC) is described. This rat hereditary cancer syndrome shares certain similarities with von Hippel-Lindau disease (VHLD). In addition to the early development of renal epithelial tumors with morphologic similarity to human RCC, rats which bear the RCC gene are predisposed to the development of secondary primary cancers later in fife. Splenic vascular proliferative lesions, including hemangiosarcoma, were seen in 23% of 14-month-old rats of both sexes that had renal tumors. At fourteen months of age, 62% of female rats with renal cell tumors had sarcomas of the lower reproductive tract of probable smooth muscle origin. Non-carrier siblings of affected animals did not have renal, reproductive, or splenic neoplasia. The finding of a specific constellation of familial neoplasms, including multicentric bilateral renal cell carcinoma, in this autosomal dominant disorder of rats suggests that this syndrome is analogous to human VHLD. In addition to its usefulness for studies of the biochemical and molecular mechanisms of renal carcinogenesis, this animal model will provide a unique tool to investigate how cancer susceptibility genes interact with environmental risk factors such as chemical carcinogens.