Lung-targeted expression of the c-Raf-1 kinase in transgenic mice exposes a novel oncogenic character of the wild-type protein

Eugen Kerkhoff, Lev M. Fedorov, Renate Siefken, Annette O. Walter, Thomas Papadopoulos, Ulf R. Rapp

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

The c-Raf-1 kinase is a downstream effector of Ras signaling. Both proteins are highly oncogenic when they are mutationally activated, but only the Ras GTPase is frequently mutated in naturally occurring tumors. Although the c-Raf-1 protein was found to be amplified in different lung cancer cell lines, overexpression of the wild-type c-Raf-1 protein was shown to be insufficient to transform cultured cells. Here we have addressed the question of whether overexpression of the wild-type c-Raf-1 kinase can induce lung cancer in mice. We show that lung-targeted expression of oncogenically activated or wild-type c-Raf-1 proteins induces morphologically indistinguishable lung adenomas in transgenic mice. Compared with mice transgenic for the activated c-Raf-1-BxB, tumor development is delayed and occurs at a lower incidence in wild-type c-Raf-1 transgenic mice. Our studies show that the c-Raf-1 expression level is a critical parameter in tumor development and should be analyzed in more detail to evaluate its potential in the induction of cancer.

Original languageEnglish (US)
Pages (from-to)185-190
Number of pages6
JournalCell Growth and Differentiation
Volume11
Issue number4
StatePublished - Apr 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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