Advertisement

ras Oncogenes pp 157-163 | Cite as

Ras-Induced Phenotypic Changes in Human Fibroblasts

  • L. Fiszer-Maliszewska
  • A. R. Kinsella

Abstract

DNA transfection studies have shown activated ras genes to transform established rodent cell lines in a dominant fashion and to co-operate with so-called nuclear oncogenes in primary cultures to give transformation (Land et al, 1983; Ruley, 1983; Reviewed Balmain, 1985). Activated ras genes have been identified in a wide variety of human tumour and human tumour cell line DNAs (Santos et al, 1982; Hall et al, 1983; Barbacid, 1986; Lowy and Willumsen, 1986; Bos et al, 1987) suggesting that the ras oncogene family (Ha-; Ki-; N) might have an important role to play in human tumourigenesis and human cell transformation. This is in part confirmed by the limited success of ras-induced in vitro human epithelial cell transformation (Yoakum et al, 1985; Rhim et al, 1985; Boukamp et al, 1986). However, when compared with rodent fibroblast cell transformation, very little is known about human cell transformation other than that it is very difficult to achieve either by the use of conventional carcinogenic agents (Kakunaga, 1978; Milo and DiPaolo, 1978; Milo et al, 1981) or by the introduction of activated ras genes. Several groups have reported the failure of an activated ras gene to transform normal human fibroblasts (Sager et al, 1983; Spandidos, 1985; Namba et al, 1988), whilst Sutherland et al (1985) showed pT24 Ha-ras to confer a high incidence of anchorage independence, but not tumourigenicity on neonate foreskin fibroblasts.

Keywords

Skin Fibroblast Normal Human Fibroblast Anchorage Independence Normal Skin Fibroblast Normal Human Skin Fibroblast 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Balmain, A., 1985, Transforming ras oncogenes and multi-stage carcinogenesis. Br. J. Cancer, 5:1CrossRefGoogle Scholar
  2. Barbacid, M., 1986, Oncogenes and human cancer. Carcinogenesis, 7: 1037PubMedCrossRefGoogle Scholar
  3. Bos, J. L., Fearon, E. R., Hamilton, S. R., de Vries, V., van Boom, J. H., Van der Eb, A. J. and Vogelstein, B., 1987, Prevalance of ras gene mutations in human colorectal cancers. Nature, 327: 293PubMedCrossRefGoogle Scholar
  4. Boukamp, P., Stanbridge, E. J., Cerutti, P. A. and Fusenig, N. E., 1986, Malignant transformation of 2 human skin keratinocyte lines by Harvey-ras oncogene. J. Invest. Dermatol, 87: 131Google Scholar
  5. Gainer, H. Stc., Schor, S. and Kinsella, A. R., 1984, Susceptibility of skin fibroblasts from individuals genetically pre-disposed to cancer to transformation by the tumour promoter 12–0-tetradecanoylphorbol-13acetate. Int. J. Cancer, 34: 349PubMedCrossRefGoogle Scholar
  6. Hall, A., Marshall, C., Spurr, N. and Weiss, R., 1983, Identification of the transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1. Nature, 303: 396PubMedCrossRefGoogle Scholar
  7. Hurlin, P. J., Fry, D. G., Maher, V. M. and McCormick, J. J., 1987, Morhplogical transformation, focus formation and anchorage independence induced in diploid human fibroblasts by expression of a transfected Ha-ras oncogene. Cancer Res, 47: 5752PubMedGoogle Scholar
  8. Kakunaga, T., 1978, Neoplastic transformation of human diploid fibroblast cells by chemical carcinogens. Proc. Natl. Acad. Sci, 75: 1334PubMedCrossRefGoogle Scholar
  9. Kinsella, A. R., 1987, The study of multi-stage carcinogenesis in retinoblastoma and familial polyposis coli patient derived skin fibroblast cell culture systems. Mutation Res, 199: 353Google Scholar
  10. Kopelovich, L., 1982, Are all diploid human strains alike? Relevance to carcinogenic mechanisms in vitro. Exp. Cell Biol, 50: 266PubMedGoogle Scholar
  11. Land, H., Parada, L. and Weinberg, R. A., 1983, Tumourigenic conversion of primary embryo fibroblasts requires at least two co-operating oncogenes. Nature, 304: 596PubMedCrossRefGoogle Scholar
  12. Lowy, D. R. and Willumsen, 1986, The ras gene family. Cancer Surveys, 5: 273Google Scholar
  13. Milo, G. E. and DiPaolo, J. A., 1978, Neoplastic transformation of human diploid cells in vitro after chemical carcinogen treatment. Nature, 275: 130PubMedCrossRefGoogle Scholar
  14. Milo, G. E., Noyes, I., Donahoe, J. and Weisbrode, S., 1981, Neoplastic transformation of human epithelial cells in vitro after exposure to chemical carcinogens. Cancer Res, 41: 5096PubMedGoogle Scholar
  15. Miyamoto, C., Chizzonite, R., Crowl, R., Rupprecht, K., Kramer, R., Schaber, M., Kumar, A., Poonain, M. and Ju, G., 1985, Molecular cloning and regulated expression of the human c-myc gene in E.coli and Saccharomyces cerevisiae: comparison of the protein products. Proc. Natl. Acad. Sci, 82: 7232PubMedCrossRefGoogle Scholar
  16. Namba, M., Nishitani, K., Fukushima, F., Kimoto, T. and Yuasa, Y., 1988, Multi-step neoplastic transformation of normal human fibroblasts by <co-60 gamma rays and Ha-ras oncogenes. Mutation Res, 199: 415PubMedCrossRefGoogle Scholar
  17. Newbold, R. E. and Overell, R. W., 1983, Fibroblast immortality is a pre-requisite for transformation by EJ c-Ha-ras oncogene. Nature, 304: 648PubMedCrossRefGoogle Scholar
  18. Rhim, J. S., Jay, G., Arnstein, P., Price, F. M., Sanford, K. K. and Aaronson, S. A., 1985, Neoplastic transformation of human epidermal keratinocytes by Ad12-SV40 and Kirsten sarcoma viruses. Science, 227: 1250PubMedCrossRefGoogle Scholar
  19. Ruley, H. E., 1983, Adenovirus early region lA enables viral and cellular transforming genes to transform primary cells in culture. Nature, 304: 602PubMedCrossRefGoogle Scholar
  20. Sager, R., Lanaka, K., Lau, C. C., Ebina, Y. and Anisowicz, A., 1983, Resistance of human cells to tumourigenesis induced by cloned transforming genes. Proc. Natl. Acad. Sci, 80: 7601PubMedCrossRefGoogle Scholar
  21. Santos, E., Tronick, S. R., Aaronson, S. A., Pulciani, S. and Barbacid, M., 1982, T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB- and Harvey-MSV transforming genes. Nature, 298: 343PubMedCrossRefGoogle Scholar
  22. Spandidos, D. A. and Wilkie, N. M., 1984, Malignant transformation of early passage rodent cells by a single mutated human oncogene. Nature. 310: 469PubMedCrossRefGoogle Scholar
  23. Spandidos, D. A., 1985, Mechanism of carcinogenesis: The role of oncogenes transcriptional enhancers and growth factors. Anticancer Res, 5: 485PubMedGoogle Scholar
  24. Stocking, C., Kollek, R., Bergholz, U. and Ostertag, W., 1986, Point mutations in the U3 region of the LTR of Moloney Murine Leukaemia virus determine disease specificity of the myeloproliferative sarcoma virus. Virology 153: 145PubMedCrossRefGoogle Scholar
  25. Sutherland, B., Bennett, P. V., Freeman, A. G., Moore, S. P. and Strickland, P. T., 1985, Transformation of human cells by DNA transfection. Proc. Natl. Acad. Sci, 82: 2399PubMedCrossRefGoogle Scholar
  26. Yoakum, G. H., Lechner, J. F., Gabrielson, E. W., Korba, B. E., Malan-Shibley, L., Willey, J. C., Valerio, M. G., Shumsudin, A. M., Trump, B. F. and Harris, C. C., 1985, Transformation of human bronchial epithelial cells transfected by Ha-ras oncogene. Science, 227: 1174PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • L. Fiszer-Maliszewska
    • 1
  • A. R. Kinsella
    • 1
  1. 1.Paterson Institute for Cancer ResearchChristie Hospital and Holt Radium InstituteManchesterUK

Personalised recommendations