Oncogene activation in multistage carcinogenesis is discussed. Results from a number of in vitro studies are cited. An understanding of the mechanisms that suppress activated ras oncogene-induced transformation by protease inhibitors is expected to shed light on the process of multistage carcinogenesis.
References
1.
1. Barbacid, M., Ras genes. (1987). Annu. Rev. Biochem.56, 779–827.
2.
2. Zarbl, H., Sukumar, S., Arthur, A.V., Martin-Zanca, D., and Barbacid, M. (1985). Direct mutagenesis of Ha-ras-1 oncogenes by N-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats. Nature315, 382–5.
3.
3. Quintanilla, M., Brown, K., Ramsden, M., and Balmain, A. (1986). Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature322, 78–80.
4.
4. Hochwalt, A.E., Solomon, J.J., and Garte, S.J. (1988). Mechanism of H-ras Oncogene Activation in Mouse Squamous Carcinoma Induced by an Alkylating Agent. Cancer Res.48, 556–558.
5.
5. Guerrero, I., Calzava, P., Mayer, A., and Pellicer, A. (1984). A molecular approach to leukemogenesis; mouse lymphomas contain an activated c-ras oncogene. Proc. Natl. Acad. Sci. USA81, 202–5.
6.
6. Reynolds, S.H., Stowers, S.J., Patterson, R.M., Maronpot, R.R., Aarsonson, S.A., and Anderson, M.W. (1987). Activated oncogenes in B6C3F1 mouse liver tumors: Implications for risk assessment. Science237, 1309–16.
7.
7. Land, H., Parada, L.F., and Weinberg, R.A. (1983). Tumorigenic Conversion of Primary Embryo Fibroblasts Requires at Least Two Cooperating Oncogenes. Nature304, 596–602.
8.
8. Hsiao, W.-L.W., Gattoni-Celli, S., and Weinstein, I.B. (1984). Oncogene-induced transformation of C3H10T 1/2 cells in enhanced by tumor promoters. Science226, 552–5.
9.
9. Dotto, G.P., Parada, L.F., and Weinberg, R.A. (1985). Specific growth response of ras-transformed embryo fibroblasts to tumor promoters. Nature318, 472–5.
10.
10. Sawey, M.J., Hood, A.T., Burns, F.J., and Garte, S.J. (1987). Activation of myc and ras oncogenes in primary rat tumors induced by ionizing radiation. Mol. Cell. Biol.7, 932–5.
11.
11. Garte, S.J., Currie, D.D., and Troll, W. (1987). Inhibition of H-ras Oncogene Transformation of NIH3T3 Cells by Protease Inhibitors. Cancer Res.47, 3159–62.