Multi-step carcinogenesis using genetically retired models

癌症是一种可遗传的体细胞疾病。环境和遗传都有助于人类癌症的起源。遗传性肾癌（RC）的Eker（Tsc 2基因突变体）大鼠模型是实验动物中特定癌症的孟德尔显性遗传易感性的实例。癌变过程看起来像一个打开的日本扇子，因为开始向几个方向生长的细胞会发展成具有许多基因异常的肿瘤，这是由扇子的边缘暗示的。为了寻找这种基因改变，我们鉴定了（Niban和Ere）在肾肿瘤中的表达比在正常肾脏中的表达更丰富。最近，我们在日本的大鼠中发现了一种新的遗传性肾癌，该大鼠被命名为“Ninon”大鼠，其易感基因（Bhd）可能是一种新的肾肿瘤抑制基因。我们提出了这些独特的模型来研究癌发生的问题，例如，多步骤致癌作用，癌症预防和治疗方法的发展，可转化为人类患者，以及环境因素如何与癌症易感基因相互作用，并讨论了肾癌发生中的原始力量和基因网络（联邦领导）。

Cancer is a heritable disorder of somatic cells. Environment and heredity both contribute to the origin of human cancer. The Eker (Tsc 2 gene mutant) rat model of hereditary renal carcinoma (RC) is an example of a Mendelian dominantly inherited predisposition to a specific cancer in an experimental animal. Carcinogenesis looks like an opened Japanese fan, because initiated cells growing in several directions will develop into tumors having many gene abnormalities, and this is suggested by the edge of the fan. To search for such genetic alterations, we identified genes (Niban and Ere) that were expressed more abundantly in renal tumors than in the normal kidney.Recently, we discovered a new hereditary renal carcinoma in the rat in Japan, and the rat was named the "Ninon" rat and its predisposing (Bhd) gene could be a novel renal tumor suppressor gene.We present these unique models for the study of problems in carcinogenesis; eg., multistep carcinogenesis, cancer prevention and the development of the therapeutic treatments which can be translated into human patients, as well as how environmental factors interact with cancer susceptibility gene(s) and discuss the primal force and gene networks (federal headship) in renal carcinogenesis.