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Mol Cell Biol. 1996 Aug;16(8):4504-11.

Cellular transformation and malignancy induced by ras require c-jun.

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  • 1Hormone Research Institute, University of California, San Francisco 94143, USA.

Abstract

ras is an important oncogene in experimental animals and humans. In addition, activated ras proteins are potent inducers of the transcription factor AP-1, which is composed of heterodimeric complexes of Fos and Jun proteins. Together with the fact that deregulated expression of some AP-1 proteins can cause neoplastic transformation, this finding suggests that AP-1 may function as a critical ras effector. We have tested this hypothesis directly by analyzing the response to activated ras in cells that harbor a null mutation in the c-jun gene. The transcriptional response of AP-1-responsive genes to activated ras is severely impaired in c-jun null fibroblasts. Compared with wild-type cells, the c-jun null cells lack many characteristics of ras transformation, including loss of contact inhibition, anchorage independence, and tumorigenicity in nude mice; these properties are restored by forced expression of c-jun. Rare tumorigenic variants of ras-expressing c-jun null fibroblasts do arise. Analysis of these variants reveals a consistent restoration of AP-1 activity. The results provide genetic evidence that c-jun is a crucial effector for transformation by activated ras proteins.

PMID:
8754851
[PubMed - indexed for MEDLINE]
PMCID:
PMC231449
Free PMC Article
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