Specific growth response of ras-transformed embryo fibroblasts to tumour promoters

Gian Paolo Dotto, Luis F. Parada, Robert A. Weinberg

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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.

Original languageEnglish (US)
Pages (from-to)472-475
Number of pages4
JournalNature
Volume318
Issue number6045
DOIs
StatePublished - Dec 1 1985

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    Paolo Dotto, G., Parada, L. F., & Weinberg, R. A. (1985). Specific growth response of ras-transformed embryo fibroblasts to tumour promoters. Nature, 318(6045), 472-475. https://doi.org/10.1038/318472a0