The role of non-ras transforming genes in chemical carcinogenesis.

Abstract

DNA transfection experiments using the NIH 3T3 mouse fibroblast cell line have demonstrated that chemically induced tumors and chemically transformed cell lines frequently contain dominant transforming genes. Although many of the genes detected using the NIH 3T3 transfection-transformation assay are activated versions of H-ras, K-ras, and N-ras, in some experimental systems activated forms of genes such as met and neu that are unrelated to ras have been observed. The activated met gene was originally detected in a human cell line that had been transformed by exposure to N-methyl-N'-nitro-N-nitrosoguanidine. Subsequent studies demonstrated that the met proto-oncogene encodes a novel growth factor receptor and that gene activation involves the production of a chimeric gene in which the regions of met encoding the extracellular and transmembrane domains of the receptor are replaced by the 5'-region of an unrelated gene called trp. The activated neu gene was detected in tumors of the nervous system that arose in mice following transplacental exposure to N-ethyl-N-nitrosourea. The neu gene also encodes a novel growth factor receptor but, in contrast to met, its activation involves a single T:A----A:T point mutation in the region of the neu gene encoding the receptor transmembrane domain. The presence of genetic alterations in chemically induced malignancies has also been assessed in cytogenetic studies and by Southern analysis of DNA from neoplastic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

A tobacco-specific carcinogen in the fetus

“…Another example is the development of nervous system tumours in mice following transplacental exposure to N-ethyl-N-nitrosourea in which the activated NEU gene was detected. This gene normally encodes a novel growth factor receptor and its activation involves a single point mutation (Cooper, 1991). Human studies of cord blood T lymphocytes from newborns following transplacental exposure to cigarette smoke, albeit passive, revealed an increased rate of mutations (deletions) in those infants of exposed mothers (Finette et al, 1998).…”

Kirsten Ras* oncogene: Significance of its discovery in human cancer research

“…The Mo-SV-specific sequence, later named mos , was found to have originated from the mouse genome and to be present in the human genome as well [67]. However, the incidence of mos mutations was low in human cancer cells, while enhanced expression was observed [68]. It was reported that mos kinase activated ERK in the Ras-Raf pathway [69].…”