Abstract
The established mouse cell line NIH 3T3 has been used with considerable success over the past three years as the basis of an in vitro transformation assay for demonstrating the presence of transfectable transforming genes in the DNA of certain human and rodent tumour cells (for review see ref. 1). In the case of the human bladder carcinoma cell lines EJ and T24, this approach has led2–4 to the molecular cloning of a transforming gene which is closely related to the rat-derived Harvey sarcoma virus oncogene, v-Ha-ras5,6. A single point mutation, which distinguishes these genes from their normal human homologue (c-Ha-ras1), is thought to be solely responsible for their transforming potential7–10. However, carcinogenesis in both humans and laboratory rodents is a multi-stage process (reviewed in ref. 11) of which the NIH 3T3 cell, already partly transformed, may represent only the penultimate stage. We therefore chose to examine the transforming effects of the EJ oncogene in a hamster fibroblast system originally developed in our laboratory to study stages in carcinogen-induced malignant transformation of normal diploid cells12. We show here that EJ c-Ha-ras-1 lacks complete transforming activity when transfected into normal fibroblasts which have a limited life-span, but can fully transform fibroblasts that have been newly ‘immortalized’ by carcinogens.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Cooper, G. M. Science 218, 801–806 (1982).
Goldfarb, M., Shimizu, K., Perucho, M. & Wigler, M. Nature 296, 404–409 (1982).
Shih, C. & Weinberg, R. A. Cell 29, 161–169 (1982).
Pulciani, S. et al. Proc. natn. Acad. Sci. U.S.A. 79, 2845–2849 (1982).
Parada, L. F., Tabin, C. J., Shih, C. & Weinberg, R. A. Nature 297, 474–478 (1982).
Santos, E. et al. Nature 298, 343–347 (1982).
Tabin, C. J. et al. Nature 300, 143–149 (1982).
Reddy, E. P., Reynolds, R. K., Santos, E. & Barbacid, M. Nature 300, 149–152 (1982).
Taparowski, E. et al. Nature 300, 762–765 (1982).
Capon, D. J. et al. Nature 302, 33–37 (1983).
Farber, E. & Cameron, R. Adv. Cancer Res. 31, 125–226 (1980).
Newbold, R. F., Overell, R. W. & Connell, J. R. Nature 299, 633–635 (1982).
Wigler, M. et al. Proc. natn. Acad. Sci. U.S.A. 76, 1373–1376 (1979).
Wigler, M. et al. Cell 16, 777–785 (1979).
O'Hare, K., Benoist, C. & Breathnach, R. Proc. natn. Acad. Sci. U.S.A. 78, 1527–1531 (1981).
Pulciani, S. et al. Nature 300, 539–542 (1982).
McCoy, M. S. et al. Nature 302, 79–81 (1983).
Balmain, A. & Pragnell, I. B. Nature 303, 72–74 (1983).
Hall, A., Marshall, C. J., Spurr, N. K. & Weiss, R. A. Nature 303, 396–400 (1983).
Pai, S. B., Steele, V. E. & Nettesheim, P. Carcinogenesis 4, 369–374 (1983).
Smith, B. L., Anisowicz, A., Chodosh, L. A. & Sager, R. Proc. natn. Acad. Sci. U.S.A. 79, 1964–1968 (1982).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Newbold, R., Overell, R. Fibroblast immortality is a prerequisite for transformation by EJ c-Ha-ras oncogene. Nature 304, 648–651 (1983). https://doi.org/10.1038/304648a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/304648a0
This article is cited by
-
Activating mutations in BRAF disrupt the hypothalamo-pituitary axis leading to hypopituitarism in mice and humans
Nature Communications (2021)
-
The effects of mutant Ras proteins on the cell signalome
Cancer and Metastasis Reviews (2020)
-
Vav1 mutations identified in human cancers give rise to different oncogenic phenotypes
Oncogenesis (2018)
-
Melanocytic nevi and melanoma: unraveling a complex relationship
Oncogene (2017)
-
The Nogo-B receptor promotes Ras plasma membrane localization and activation
Oncogene (2017)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
