Multi-step carcinogenesis using genetically retired models

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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.