Skip to main content
SpringerLink
Log in

ras Transfection and expression does not induce progression from tumorigenicity to metastatic ability in mouse LTA cells

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Studies testing the ability of a transfected ras oncogene to confer metastatic properties on non-metastatic cells have yielded conflicting results. Most of these studies have used recipient cells at early stages of progression (primary or immortalized, non-tumorigenic lines). In this study we tested the ability of the T24-H-ras oncogene to induce progression of tumorigenic, non-metastatic, murine LTA cells to a metastatic phenotype. Metastatic ability was assessed in complementary assays in two immune-deficient hosts, nude mice (after s.c. injection) and chick embryos (after i.v. injection), to determine if ras transfection affected metastatic properties in hosts lacking an intact immune system. Even with greatly elevated levels of ras p21 protein, pools of ras-transfected cells as well as individual clonal populations remained non-metastatic in both hosts. Serial in vivo passaging did not consistently enhance for either ras expression or metastatic ability. We conclude that expression of an activated ras oncogene in LTA cells does not induce progression from a tumorigenic to a metastatic phenotype. These results are in marked contrast to those obtained for ras expression in most other cell types. High levels of expression of an activated ras oncogene thus do not always promote progression from tumorigenicity to metastatic ability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Balmain, A., and Brown, K., 1988, Oncogene activation in chemical carcinogenesis. Advances in Cancer Research, 51, 147–182.

    Google Scholar 

  2. Barbacid, M., 1987, ras genes. Annual Review of Biochemistry, 56, 779–827.

    Google Scholar 

  3. Bell, J. C., Jardine, K., and McBurney, M. W., 1986, Lineage-specific transformation after differentiation of multipotential murine stem cells containing a human oncogene. Molecular and Cellular Biology, 6, 617–625.

    Google Scholar 

  4. Bondy, G. P., Wilson, S., and Chambers, A. F., 1985, Experimental metastatic ability of H-ras-transformed NIH3T3 cells. Cancer Research, 45, 6005–6009.

    Google Scholar 

  5. Bradley, M. O., Kraynak, A. R., Storer, A. R., and Gibbs, J. B., 1986, Experimental metastasis in nude mice of NIH/3T3 cells containing various ras genes. Proceedings of the National Academy of Sciences (U.S.A.), 83, 5277–5281.

    Google Scholar 

  6. Chadwick, D. E., and Lagarde, A. E., 1988, Coincidential acquisition of growth autonomy and metastatic potential during the malignant transformation of factordependent CCL39 lung fibroblasts. Journal of the National Cancer Institute, 80, 318–325.

    Google Scholar 

  7. Chambers, A. F., and Ling, V., 1984, Selection for experimental metastatic ability of heterologous tumor cells in the chick embryo after DNA-mediated transfer. Cancer Research, 44, 3970–3975.

    Google Scholar 

  8. Chambers, A. F., and Tuck, A. B., 1988, Oncogene transformation and the metastatic phenotype. Anticancer Research, 8, 861–872.

    Google Scholar 

  9. Chambers, A. F., Denhardt, G. H., and Wilson, S. M., 1990, Ras-transformed NIH 3T3 cell lines, selected for metastatic ability in chick embryos, have increased proportions of p21-expressing cells and are metastatic in nude mice. Invasion Metastasis (in press).

  10. Chaney, W. G., Howard, D. R., Pollard, J. W., Sallustio, S., and Stanley, P., 1986, High-frequency transfection of CHO cells using polybrene. Somatic Cell and Molecular Genetics, 12, 237–244.

    Google Scholar 

  11. Collard, J. G., Schijven, J. F., and Roos, E., 1987, Invasive and metastatic potential induced by ras-transfection into mouse BW5147 T-lymphoma cells. Cancer Research, 47, 754–759.

    Google Scholar 

  12. Earle, W. R., 1943, Production of malignancy in vitro. IV. The mouse fibroblast cultures and changes seen in the living cells. Journal of the National Cancer Institute, 4, 165–212.

    Google Scholar 

  13. Egan, S. E., McClarty, G. A., Jarolim, L., Wright, J. A., Spiro, I., Hager, G., and Greenberg, A. H., 1987, Expression of H-ras correlates with metastatic potential: evidence for direct regulation of the metastatic phenotype in 10T1/2 and NIH 3T3 cells. Molecular and Cellular Biology, 7, 830–837.

    Google Scholar 

  14. Feldman, M., and Eisenbach, L., 1988, Genes controlling the metastatic phenotype. Cancer Surveys, 7, 555–629.

    Google Scholar 

  15. Furth, M. E., Davis, L. J., Fleurdelys, B., and Scolnick, E. M., 1982, Monoclonal antibodies to the p21 products of the transforming gene of Harvey murine sarcoma virus and of the cellular ras gene family. Journal of Virology (Washington), 43, 294–304.

    Google Scholar 

  16. Galand, P., Jacobovitz, D., and Alexandre, K., 1988, Immunohistochemical detection of c-Ha-ras oncogene p21 product in pre-neoplastic and neoplastic lesions during hepatocarcinogenesis in rats. International Journal of Cancer, 41, 155–161.

    Google Scholar 

  17. Garin Chesa, P., Rettig, W. J., Melamed, M. R., Old, L. J., and Niman, H. L., 1987, Expression of p21ras in normal and malignant human tissues: Lack of association with proliferation and malignancy. Proceedings of the National Academy of Sciences (U.S.A.), 84, 3234–3238.

    Google Scholar 

  18. Gilbert, P. X., and Harris, H., 1988, The role of the ras oncogene in the formation of tumors. Journal of Cell Science, 90, 433–446.

    Google Scholar 

  19. Greenberg, A. H., Egan, S. E., Jarolim, L., and Wright, J. A., 1987, NK sensitivity of H-ras transfected fibroblasts is transformation-independent. Cellular Immunology, 109, 444–450.

    Google Scholar 

  20. Greig, R. G., Koestler, T. P., Trainer, D. L., Corwin, S. P., Miles, L., KLINE, T., Sweet, R., Yokoyama, S., and Poste, G., 1985, Tumorigenic and metastatic properties of ‘normal’ and ras-transfected NIH/3T3 cells. Proceedings of the National Academy of Sciences (U.S.A.), 82, 3698–3701.

    Google Scholar 

  21. Hanna, N., Davis, T. W., and Fidler, I. J., 1982, Environmental and genetic factors determine the level of NK activity of nude mice and affect their suitability as models for experimental metastasis. International Journal of Cancer, 30, 371–376.

    Google Scholar 

  22. Harris, J. F., Chambers, A. F., and Tam, A. S. K., 1990, Some ras-transformed cells have increased radiosensitivity and decreased repair of sublethal radiation damage. Somatic Cell and Molecular Genetics, 16, 39–48.

    Google Scholar 

  23. Hill, S. A., Wilson, S., and Chambers, A. F., 1988, Clonal heterogeneity, experimental metastatic ability, and p21 expression in H-ras-transformed NIH 3T3 cells. Journal of the National Cancer Institute, 80, 484–490.

    Google Scholar 

  24. Hunter, T., 1984, Oncogenes and proto-oncogenes: how do they differ? Journal of the National Cancer Institute, 73, 773–786.

    Google Scholar 

  25. Hurlin, P. J., Maher, V. M., and McCormick, J. J., 1989, Malignant transformation of human fibroblasts caused by expression of a transfected T24 Hras oncogene. Proceedings of the National Academy of Sciences (U.S.A.), 86, 187–191.

    Google Scholar 

  26. Johnson, P. W., Baubock, C., and Roder, J. C., 1985, Transfection of a rat cell line with the v-Ki-ras oncogene is associated with enhanced susceptibility to natural killer cell lysis. Journal of Experimental Medicine, 162, 1732–1737.

    Google Scholar 

  27. Johnson, P. W., Trimble, W. S., Hozumi, N., and Roder, J. C., 1987, Enhanced lytic susceptibility of Ha-ras transformants after oncogene induction is specific to activated NK cells. Journal of Immunology, 138, 3996–4003.

    Google Scholar 

  28. Kahn, P., Simon, R. S., Klein, A. S., and Shin, S., 1980, Tumor formation by transformed cells in nude mice. Cold Spring Harbor Symposium on Quantitative Biology, 44, 695–702.

    Google Scholar 

  29. , S., Dubbs, D. R., Piekarski, L. J., and Hsu, T. C., 1963, Deletion of thymidine kinase activity from L cells resistant to bromodeoxyuridine. Experimental Cell Research, 31, 97–312.

    Google Scholar 

  30. Klein, G., Bregula, U., and Wiener, F., 1971, The analysis of malignancy by cell fusion: I. Hybrids between tumour cells and L cell derivatives. Journal of Cell Science, 8, 659–672.

    Google Scholar 

  31. Klein, G., and Klein, E., 1986, Conditioned tumorigenicity of activated oncogenes. Cancer Research, 46, 3211–3224.

    Google Scholar 

  32. Klein, G., 1987, The approaching era of the tumor suppressor genes. Science, 238, 1539–1545.

    Google Scholar 

  33. Klein, G., 1988, Tumor suppressor genes. Journal of Cell Science(Suppl.), 10, 171–180.

    Google Scholar 

  34. Land, H., Parada, L. F., and Weinberg, R. A., 1983, Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature, 304, 596–602.

    Google Scholar 

  35. Land, H., Chen, A. C., Morgenstern, J. P., Parada, L. F., and Weinberg, R. A., 1986, Behavior of myc and ras oncogenes in transformation of rat embryo fibroblasts. Molecular and Cellular Biology, 6, 1917–1925.

    Google Scholar 

  36. Layton, M. G., and Franks, L. M., 1986, Selective suppression of metastasis but not tumorigenicity of a mouse lung carcinoma by cell hybridization. International Journal of Cancer, 37, 723–730.

    Google Scholar 

  37. Marshall, C. J., 1988, The ras oncogenes. Journal of Cell Science(Suppl.), 10, 157–169.

    Google Scholar 

  38. Muschel, R. J., Williams, J. E., Lowy, D. R., and Liotta, L. A., 1985, Harvey ras induction of metastatic potential depends upon oncogene activation and the type of recipient cell. American Journal of Pathology, 121, 1–8.

    Google Scholar 

  39. Muschel, R., and Liotta, L. A., 1988, Role of oncogenes in metastases. Carcinogenesis, 9, 705–710.

    Google Scholar 

  40. Nakagawa, T., Mabry, M., De Bustros, A., Ihle, J. N., Nelkin, B. D., and Baylin, S. B., 1987, Introduction of v-Ha-ras oncogene induces differentiation of cultured human medullary thyroid carcinoma cells. Proceedings of the National Academy of Sciences (U.S.A.), 84, 5923–5927.

    Google Scholar 

  41. Nelkin, B., Borges, M., Mabry, M., and Baylin, S., 1989, Increased c-jun oncogene expression in mammalian cells transformed or differentiated by ras oncogenes. Proceedings of the American Association for Cancer Reasearch, 30, 434.

    Google Scholar 

  42. Noda, M., Ko, M., Ogura, A., Liu, D. G., Amano, T., Takano, T., and Ikawa, Y., 1985, Sarcoma viruses carrying ras oncogenes induce differentiation-associated properties in a neuronal cell line. Nature, 318, 73–75.

    Google Scholar 

  43. Ohuchi, N., Thor, A., Page, D. L., Hand, P. H., H. CALTER, S. A., and Schlom, J., 1986, Expression of the 21,000 molecular weight ras protein in a spectrum of benign and malignant human mammary tissues. Cancer Research, 46, 2511–2519.

    Google Scholar 

  44. Pozzatti, R., Muschel, R., Williams, J., Padmanabhan, R., Howard, B., Liotta, L., and Khoury, G., 1986, Primary rat embryo cells transformed by one or two oncogenes exhibit different metastatic potentials. Science, 232, 223–227.

    Google Scholar 

  45. Price, J. E., Aukerman, S. L., Ananthaswamy, H. N., MCIntyre, B. W., Schackert, G., Schackert, H. K., and Fidler, I. J., 1989, Metastatic potential of cloned murine melanoma cells transfected with activated c-Ha-ras. Cancer Research, 49, 4274–4281.

    Google Scholar 

  46. Radinsky, R., Kraemer, P. M., Raines, M. A., Kung, H. J., and Culp, L. A., 1987, Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c3T3 cells during malignant tumor progression. Proceedings of the National Academy of Sciences (U.S.A.), 84, 5143–5147.

    Google Scholar 

  47. Sager, R., 1986, Genetic suppression of tumor formation: A new frontier in cancer research. Cancer Research, 46, 1573–1580.

    Google Scholar 

  48. Sharp, A. K., and Colston, M. J., 1984, The regulation of macrophage activity in congenitally athymic mice. European Journal of Immunology, 14, 102–105.

    Google Scholar 

  49. Southern, P. J., and Berg, P., 1982, Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV-40 early region promotor. Journal of Molecular and Applied Genetics, 1, 327–341.

    Google Scholar 

  50. Spandidos, D. A., and Wilkie, N. M., 1984, Malignant transformation of early passage rodent cells by a single mutated human oncogene. Nature, 310, 469–475.

    Google Scholar 

  51. Spandidos, D. A., and Anderson, M. L. M., 1989, Oncogenes and onco-suppressor genes: Their involvement in cancer. Journal of Pathology, 157, 1–10.

    Google Scholar 

  52. Thorgeirsson, U. P., Turpeenniemi-Hujanen, T., Williams, J. E., Weston, E. H., Heilman, C. A., Talmadge, J. E., and LIOTTA, L. A., 1985, NIH/3T3 cells transfected with human tumor DNA containing activated ras oncogenes express the metastatic phenotype in nude mice. Molecular and Cellular Biology, 5, 259–262.

    Google Scholar 

  53. Trimble, W. S., Johnson, P. W., Hozumt, N., and Roder, J. C., 1986, Inducible cellular transformation by a metallothionein-ras hybrid oncogene leads to natural killer cell susceptibility. Nature, 321, 782–784.

    Google Scholar 

  54. Tsunokawa, Y., Esumi, H., Sasaki, M. S., Mori, M., Sakamoto, H., Terada, M., and Sugimura, T., 1984, Integration of v-ras H does not necessarily transform an immortalized murine cell line. Gann, 75, 732–736.

    Google Scholar 

  55. Vousden, K. H., and Marshall, C. J., 1984, Three different activated ras genes in mouse tumors: Evidence for oncogene activation during progression of a mouse lymphoma, EMBO Journal, 3, 913–917.

    Google Scholar 

  56. Vousden, K. H., Eccles, S. A., Purvies, J., and Marshal, C. J., 1986, Enhanced spontaneous metastasis of mouse carcinoma cells transfected with an activated c-H-ras-1 gene. International Journal of Cancer, 37, 425–433.

    Google Scholar 

  57. Waghorne, C., Kerbel, R. S., and Breitman, M. L., 1987, Metastatic potential of SP1 mouse mammary adenocarcinoma cells is differentially induced by activated and normal forms of c-H-ras. Oncogene, 1, 149–156.

    Google Scholar 

  58. Weinberg, R. A., 1985, The action of oncogenes in the cytoplasm and nucleus. Science, 230, 770–776.

    Google Scholar 

  59. Wyllie, A. H., Rose, K. A., Morris, R. G., Steel, C. M., Foster, E., and Spandidos, D. A., 1987, Rodent fibroblast tumours expressing human myc and ras genes: growth, metastasis, and endogenous oncogene expression. British Journal of Cancer,56, 251–259.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. London Regional Cancer Centre, 790 Commissioners Road East, N6A 4L6, London, Ontario, Canada

    A. B. Tuck, S. M. Wilson & A. F. Chambers

  2. Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada

    A. B. Tuck & A. F. Chambers

  3. Department of Oncology, University of Western Ontario, London, Ontario, Canada

    A. F. Chambers

Authors
  1. A. B. Tuck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. M. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. F. Chambers
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tuck, A.B., Wilson, S.M. & Chambers, A.F. ras Transfection and expression does not induce progression from tumorigenicity to metastatic ability in mouse LTA cells. Clin Exp Metast 8, 417–431 (1990). https://doi.org/10.1007/BF00058153

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00058153

Keywords

Search

Navigation