title: Lung-targeted expression of the c-Raf-1 kinase in transgenic mice exposes a novel oncogenic character of the wild-type protein.
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.
authors.affiliation: Institut für medizinische Strahlenkunde und Zellforschung, Universität Würzburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Kerkhoff
authors.forename: L M
authors.initials: LM
authors.lastname: Fedorov
authors.forename: R
authors.initials: R
authors.lastname: Siefken
authors.forename: A O
authors.initials: AO
authors.lastname: Walter
authors.forename: T
authors.initials: T
authors.lastname: Papadopoulos
authors.forename: U R
authors.initials: UR
authors.lastname: Rapp
mesh_terms: D000236:Adenoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000818:Animals; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011510:Proteolipids / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf / Q000032:analysis / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics
chemical_list: D011510:Proteolipids; D011663:Pulmonary Surfactants; D011993:Recombinant Fusion Proteins; D019908:Proto-Oncogene Proteins c-raf