Differentiation can convey resistance to transformation by activated ras oncogene

Nonterminal cellular differentiation has recently been shown to induce transformed cells to revert to a benign state and to become resistant to retransformation by chemical and physical carcinogens without limiting their proliferative potential. Nonterminal differentiation also induces native 3T3 T mesenchymal stem cells to become resistant to transformation induced by numerous chemical and physical carcinogens. This characteristic has been designated anticancer activity. In the current study, experiments show that cells expressing differentiation-associated anticancer activity are also resistant to transformation by the activated ras (EJras) oncogene. Resistance to EJras transformation is shown not to result from a reduced efficiency of DNA transfection nor from reduced integration of EJras into the genome. Moreover, the results show that the EJras oncogene product can be expressed in cells demonstrating anticancer activity. Nonterminal cellular differentiation, therefore, induces resistance to transformation caused by activated ras oncogene as well as to numerous physical and chemical carcinogens.