Complex effects of Ras proto-oncogenes in tumorigenesis

Roberto Diaz, Lluis Lopez-Barcons, Daniel Ahn, Antonio Garcia-Espana, Andrew Yoon, Jeremy Matthews, Ramon Mangues, Roman Perez-Soler, Angel Pellicer

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Abstract

Ras proteins have been found mutated in about one-third of human tumors. In vitro, Ras has been shown to regulate distinct and contradictory effects, such as cellular proliferation and apoptosis. Nonetheless, the effects that the wild-type protein elicits in tumorigenesis are poorly understood. Depending on the type of tissue, Ras proto-oncogenes appear to either promote or inhibit the tumor phenotype. In this report, we treated wild-type and N-ras knockout mice with 3-methylcholanthrene (MCA) to induce fibrosarcomas and found that MCA is more carcinogenic in wild-type mice than in knockout mice. After injecting different doses of a tumorigenic cell line, the wild-type mice exhibited a shorter latency of tumor development than the knockouts, indicating that there are N-ras-dependent differences in the stromal cells. Likewise, we have analyzed B-cell lymphomas induced by either N-methylnitrosourea or by the N-ras oncogene in mice that over-express the N-ras proto-oncogene and found that the over-expression of wild-type N-ras is able to increase the incidence of these lymphomas. Considered together, our results indicate that Ras proto-oncogenes can enhance or inhibit the malignant phenotype in vivo in different systems.

Original languageEnglish (US)
Pages (from-to)535-539
Number of pages5
JournalCarcinogenesis
Volume25
Issue number4
DOIs
StatePublished - Apr 2004

ASJC Scopus subject areas

  • Cancer Research

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    Diaz, R., Lopez-Barcons, L., Ahn, D., Garcia-Espana, A., Yoon, A., Matthews, J., Mangues, R., Perez-Soler, R., & Pellicer, A. (2004). Complex effects of Ras proto-oncogenes in tumorigenesis. Carcinogenesis, 25(4), 535-539. https://doi.org/10.1093/carcin/bgh026