A study of mechanisms of carcinogenesis by gene transfer of oncogenes into mammalian cells

Abstract

Recent work has shown that individual oncogenes can be involved in several steps of the multistage process of carcinogenesis. Evidence comes from studies on the expression of cloned oncogenes transfected into early passage mammalian cells and into immortalized non-tumorigenic cell lines. Transformation of epithelial cells in vitro with cloned cellular and viral oncogenes is of special interest since most human tumors are of epithelial origin. An important aspect of cell transformation by oncogenes is the induction of transforming growth factors (TGFs). The role of oncogenes in differentiation has been examined by introducing the human myc and mutant T24 Ha-ras1 genes into mouse erythroleukemic cells which were then induced to differentiate. In several clones differentiation was inhibited by myc or ras genes. Studies are reported using oncogenes linked to transcriptional control elements that can be regulated in vitro, such as the human metallothionein (hMT-IIA) promoter region, by cadmium and dexamethasone. Phenotypic properties of transfectants including morphological transformation, anchorage dependence and TGF release are shown to be dependent on the regulators of the hMT-IIA control region.