Enhancement of Oncogene-Mediated Transformation in Cloned Rat Embryo Fibroblast (CREF) Cells by 3-Aminobenzamide

Abstract

The carcinogenic process involves a complex series of genetic alterations in the evolving tumor cell resulting in changes in genes which induce both positive (oncogene) and negative (tumor suppressor) control of cellular proliferation (1-3). In vitro studies employing rat embryo fibroblast cells and more recently in vivo studies using transgenic mice have provided convincing evidence that specific oncogenes can cooperate in inducing both cellular transformation and the development of specific neoplasms (1-3). Based primarily on data obtained using early passage and established rodent cells it appears that oncogenes which act in the nucleus can cooperate most efficiently with oncogenes which act in the cytoplasm (1,3). Cooperative interactions between nuclear oncogenes, such as myc, N-myc, mutant p53, fos, jun, adenovirus (Ad) E1A, polyomavirus and SV40 large T antigens, papillomavirus E7 and tax of human T cell leukemia virus type 1, and cytoplasmic oncogenes, such as Ha-ras, Ki-ras, N-ras, src and polyomavirus middle T antigen, have been described (reviewed in 1,3). However, there are examples in which two nuclear oncoproteins (4) or two cytoplasmic oncoproteins (5) can cooperate in inducing transformation of rat embryo fibroblasts.