A Human Renal Epithelial Multistep Model of in vitro Carcinogenesis

Abstract

Experimental in vitro models to transform human cells should provide clues to the mechanisms of development of human tumors and could identify agents that might cause human cancer. Studies of neoplastic transformation in epithelial cells are critical to an understanding of human cancer since more than 80% of human cancers are of epithelial origin. Human cells are highly resistant to changes in the mechanisms that limit their in vitro life span (1,2). Thus, there are few reports describing carcinogen-induced neoplastic transformation of epithelial cells (3,4). In vitro models of multistep transformation provide the opportunity to study cells at different stages of the transformation process. Studies strongly suggest that neoplastic transformation, both in vivo and in vitro, is a multistep process involving events of initiation, promotion and progression (5). Cellular immortality is considered to be one of the first phenotypic changes in this process and can be induced in primary cells by chemical carcinogens or by oncogene transfection. The conversion to the malignant stage is the second critical step. At least some of these stages may involve dominantly-acting genes. There is also evidence that loss or inactivation of several tumor suppressor genes is required for the the initation or progression of certain tumors.