Gene Amplification During Stages of Carcinogenesis

  • Joseph Locker
Part of the Basic Life Sciences book series (BLSC, volume 57)


Models of carcinogenesis have developed from extensive observation of clinical and experimental systems. (This summary is based on Pitot, 1981.) The related concepts of promotion and progression describe an essential feature of carcinogenesis, the gradual change from a normal cell to a tumor composed of proliferating, invading, metastasizing cells. Promotion is the gradual conversion of undetectable initiated cells to tumors without the continuing action of a carcinogen. Promotion requires distinct agents and involves both cell proliferation and gradually changing cell properties. In other words, promotion is the process by which an initiated cell evolves from a state of homeostatically regulated proliferation to a state of inadequately regulated proliferation. However, the appearance of a tumor is not really an endpoint in this process, and the more general term, progression, refers to the continuous evolution in characters both before and after a tumor has formed.


Gene Amplification Liver Regeneration Replication Fork Burkitt Lymphoma Dhfr Gene 
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  1. Bonilla, M., Ramirez, M., Lopez-Cueto, J., and Gariglio, P., 1988, In vivo amplification and rearrangement of c-myc oncogene in human breast tumors, J. Natl. Cancer Inst., 80:665–671.PubMedCrossRefGoogle Scholar
  2. Chandar, N., Amenta, J., Kandala, J. C., and Lombardi, B., 1987, Liver cell turnover in rats fed a choline-devoid diet, Carcinogenesis, 8:669–673.PubMedCrossRefGoogle Scholar
  3. Chandar, N., and Lombardi, B., 1988, Liver cell proliferation and incidence of hepatocellular carcinomas in rats fed consecutively a choline-devoid and a choline-supplemented diet, Carcinogenesis, 9:259–263.PubMedCrossRefGoogle Scholar
  4. Chandar, N., Lombardi, B., and Locker, J., 1989, C-Myc gene amplification in liver tumors of rats fed a choline devoid diet, Proc. Natl. Acad. Sci., U.S.A., in press.Google Scholar
  5. Cole, M. D., 1986, The myc oncogene: its role in transformation and differentiation, Ann. Rev. Genet., 361-384.Google Scholar
  6. Colletta, G., Cirafici, A. M., and Vecchio, G., 1986, Induction of the c-fos oncogene by thyrotropic hormone in rat thyroid cells in culture, Science 233:456–460.CrossRefGoogle Scholar
  7. Edwards, M. J., and Taylor, A. M. R., 1980, Unusual levels of (AFP-ribose)n and DNA synthesis in ataxia telangiectasia cells following gamma-ray irradiation, Nature, 287:745–747.PubMedCrossRefGoogle Scholar
  8. Fahrlander, P. D., and Marcu, K. B., 1986, Regulation of c-myc gene expression in normal and transformed mammalian cells, in: “Oncogenes and Growth Control,” P. Kahn, and T. Graf, eds., Springer, Berlin.Google Scholar
  9. Kelly, K., Cochran, B. H., Stiles, C. D., and Leder, P., 1983, Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor, Cell, 35:603–610.PubMedCrossRefGoogle Scholar
  10. Locker, J., and Crawford, N., 1989, Nuclear oncogenes in hepatoma cell lines, Submitted for publication.Google Scholar
  11. Piechaczyk, M., Blanchard, J.-M., and Jeanteur, P., 1987, c-myc gene regulation still holds its secret, Trends Genet., 3:47–51.CrossRefGoogle Scholar
  12. Pitot, H. C., 1981, “Fundamentals of Oncology,” Dekker, New York.Google Scholar
  13. Schimke, R. T., 1984, Gene amplification, drug resistance, and cancer, Cancer Res., 44:1735–1742.PubMedGoogle Scholar
  14. Schimke, R. T., Sherwood, S. W., Hill, A. B., and Johnston, R. N., 1986, Overreplication and recombination of DNA in higher eukaryotes: Potential consequences and biological implications, Proc. Natl. Acad. Sci., U.S.A., 83:2157–2161.PubMedCrossRefGoogle Scholar
  15. Schweinfest, C. W., Fijiwara, S., Lau, L. F., and Papas, T. S., 1988, c-myc can induce expression of G0/G1 transition genes, Mol. Cell. Biol., 8:3080–3087.PubMedGoogle Scholar
  16. Thompson, N. L., Mead, J. E., Braun, L., Goyette, M., Shank, P. R., and Fausto, N., 1986, Sequential protooncogene expression during rat liver regeneration, Cancer Res., 46:3111–3117.PubMedGoogle Scholar
  17. Van Hoff, D. D., Needhan-YanDevanter, D. R., Yucel, J., Windle, B. E., and Wahl, G. M., 1988, Amplified human MYC oncogenes localized to replicating submicroscopic circular DNA molecules, Proc. Natl. Acad. Sci., U.S.A., 85:4804–4808.CrossRefGoogle Scholar
  18. Varley, J. M., Swallow, J. E., Brammer, W. J., Whittaker, J. L., and Walker, R. A., 1987, Alterations to either c-erb B-2 or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis, Oncogene 1:423–430.PubMedGoogle Scholar
  19. Yokoyama, S., Sells, M. A., Reddy, T. V., and Lombardi, B., 1985, Hepatocarcinogenic and promoting action of a choline-devoid diet in the rat, Cancer Res., 45:2834–2842.PubMedGoogle Scholar
  20. Zimmerman, K. A., Yancopoulos, G. D., Collum, R. G., Smith, R. K., Kohl, N. E., Denis, K. A., Nau, M. M., Witte, O. N., Toran-Allerand, D., Gee, C. E., Minna, J. D. and Alt, F. W., 1986, Differential expression of myc family genes during murine development, Nature, 319:780–783.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Joseph Locker
    • 1
  1. 1.Department of PathologyUniversity of PittsburghPittsburghUSA

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