Abstract
Chemical carcinogenesis is a process involving multiple steps, as shown in several in vivo experimental systems1. Two early steps have been well characterized: initiation, achieved by a single, subthreshold dose of a carcinogen, and promotion, induced by repetitive treatments with a non-carcinogenic tumour promoter. At the cellular level, establishment of the transformed phenotype is also a multi-step process and activation of several, independent genes appears to be required2–4. Here we show that, like initiated cells, primary rat embryo fibroblasts (REFs) containing a ras but not a myc oncogene, are strongly and specifically stimulated to grow by tumour promoters. In the presence of these promoters, ras-containing REFs acquire the ability to overgrow normal cells in the monolayer and to form foci with 100% efficiency. Similar to the in vivo situation, promoter effects can be blocked by the concomitant application of retinoic acid.
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
Hecker, H., Fusenig, N. E., Kunz, W., Marks, F. & Thielman, H. W. (eds) Carcinogenesis Vol. 7 (Raven, New York, 1982).
Land, H., Parada, L. F. & Weinberg, R. A. Nature 304, 596–602 (1983).
Ruley, E. H. Nature 304, 602–606 (1983).
Newbold, R. F. & Overell, R. W. Nature 304, 648–651 (1983).
Berenblum, I. in Cancer: A Comprehensive Treatise Vol. 1 (ed. Becker, F. F.) 323–344 (Plenum, New York, 1975).
Boutwell, R. K. Prog. exp. Tumor Res. 4, 207–250 (1964).
Hennings, H. et al. Nature 304, 67–69 (1983).
Southern, P. J. & Berg, P. J. molec. appl. Genet. 1, 327–341 (1982).
Mann, R., Mulligan, R. C. & Baltimore, D. Cell 33, 153–159 (1983).
Dhar, R. et al. Science 217, 934–937 (1982).
Cepko, C. L., Roberts, B. E. & Mulligan, R. C. Cell 37, 1053–1062 (1984).
Nishizuka, Y. Nature 308, 693–698 (1984).
Verma, A. K., Rice, H. M., Shapos, B. G. & Boutwell, R. K. Cancer Res. 38, 793–801 (1978).
Slaga, T. J., Fischer, S. M., Nelson, K. & Gleason, G. L. Proc. natn. Acad. Sci. U.S.A. 77, 3659–3663 (1980).
Fürstenberger, G., Berry, D. L., Sorg, B. & Marks, F. Proc. natn. Acad. Sci. U.S.A. 78, 7722–7726 (1981).
Castagna, M. et al. J. biol. Chem. 257, 7847–7851 (1982).
Land, H., Parada, L. F. & Weinberg, R. A. Science 222, 771–778 (1983).
Yuspa, S. H., Kilkenny, A. E., Stanley, J. & Luchti, U. Nature 314, 459–462 (1985).
Baimain, A. & Pragnell, I. B. Nature 303, 72–74 (1983).
Balmain, A., Ramsden, M., Bowden, G. T. & Smith, J. Nature 307, 658–660 (1984).
Zarbl, H., Sukumar, S., Arthur, A. V., Martin-Zanca, D. & Barbacid, M. Nature 315, 382–385 (1985).
Connan, G., Rassoulzadegan, M. & Cuzin, F. Nature 314, 277–279 (1985).
Kelly, K., Cochran, B. H., Stiles, C. D. & Leder, P. Cell 35, 603–610 (1983).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Paolo Dotto, G., Parada, L. & Weinberg, R. Specific growth response of ras-transformed embryo fibroblasts to tumour promoters. Nature 318, 472–475 (1985). https://doi.org/10.1038/318472a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/318472a0
This article is cited by
-
Blocking anaplerotic entry of glutamine into the TCA cycle sensitizes K-Ras mutant cancer cells to cytotoxic drugs
Oncogene (2015)
-
Protein kinase C and other diacylglycerol effectors in cancer
Nature Reviews Cancer (2007)
-
Downregulating PKC δ provides a PI3K/Akt-independent survival signal that overcomes apoptotic signals generated by c-Src overexpression
Oncogene (2002)
-
Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation
Nature (1997)
-
Inositol trisphosphate and calcium signalling
Nature (1993)
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.
