| Abstract: |
Epidemiological surveys of occurrence of human neoplastic disease as well as in‐vitro and in‐vivo experimental models indicate that tumorigenesis is a multistep process involving independent genetic events.1‐3 In particular, studies with retroviruses and cloned oncogenes demonstrate that cooperation between oncogenes is required for full transformation of primary embryo cells in culture.4–8 Differences in response to growth factors can be observed between normal cells, which are capable of limited replication and are poorly transformable, and established cell lines, which can be more easily transformed by transfer of cloned oncogenes or exposure to carcinogens.9 Recent reports have provided evidence for effects of some oncogenes at specific points along biochemical pathways that regulate mitosis.10–13 For example, altered expression of the myc gene has been implicated in stimulation of cell growth in response to competence‐inducing growth factors in normal cells and deregulation of cell growth in some neoplastic cells.14–16 Mouse C3H10T1/2 cells have been widely used in in‐vitro transformation studies with chemicals and radiation.17,18 Several lines of evidence are suggestive of more than a single genetic event occurring before cells become able to overgrow the normal monolayer. 19–22 After carcinogenic treatment the appearance of foci of transformed cells is dependent upon proliferation of the initiated cell population, suggesting the requirement for a stochastic event in progression toward a transformed phenotype.23,24 Here we discuss results obtained by introducing the c‐myc coding region via a murine retroviral vector into mouse C3H10T1/2 and rat F2408 cells. We observe that constitutive c‐myc expression promotes growth in semisolid media and enhances responsiveness to PDGF, EGF, FGF, and TGF‐β. Introduction of an exogenous c‐myc gene into C3H10T1/2 does not result in cells that are tumorigenic. However, the expression of an exogenous myc gene increases the tumorigenicity of C3H cells carrying a mutated ras oncogene. We also observed that C3H10T1/2 cells expressing an exogenous myc gene are more efficiently transformed upon radiation or chemical carcinogen treatment. Copyright © 1987, Wiley Blackwell. All rights reserved |
