Differentiation can convey resistance to transformation by activated ras oncogene
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C Y Tzen1, P B Maercklein, R E Scott
1Department of Pathology, University of Tennessee Health Science Center, Memphis 38163.
Abstract:
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.
Insights
Nonterminal cellular differentiation confers resistance to carcinogen-induced cell transformation and oncogene-driven cancer. This anticancer activity protects cells from chemical, physical carcinogens, and activated ras oncogene transformation.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Oncology
Background:
- Nonterminal cellular differentiation can revert transformed cells to a benign state.
- This differentiation confers resistance to retransformation by chemical and physical carcinogens.
- This protective characteristic is termed anticancer activity.
Purpose of the Study:
- To investigate if anticancer activity induced by nonterminal differentiation also confers resistance to oncogene-induced transformation.
- To determine the mechanism of resistance to activated ras (EJras) oncogene transformation in differentiated cells.
Main Methods:
- Utilized 3T3 T mesenchymal stem cells and transformed cell lines.
- Assessed resistance to transformation by chemical, physical carcinogens, and the EJras oncogene.
- Investigated DNA transfection efficiency and EJras integration into the genome.
Main Results:
- Cells expressing differentiation-associated anticancer activity were resistant to EJras transformation.
- Resistance was not due to reduced DNA transfection or EJras integration.
- The EJras oncogene product was expressed in cells with anticancer activity.
Conclusions:
- Nonterminal cellular differentiation induces resistance to transformation by activated ras oncogene.
- Anticancer activity protects against a broad range of transforming agents, including oncogenes.