title: Identification and characterization of collaborating oncogenes in compound mutant mice.
abstract: We have used proviral tagging in tumor-prone transgenic mice to identify collaborating oncogenes and genes contributing to tumor progression. This has yielded a series of oncogenes that could be assigned to different complementation groups in transformation: the myc, Pim, Bmi1, and Frat1 complementation groups. Frat1 is involved in tumor progression and appears to function in the Wnt signaling pathway. Overexpression of Fratl confers a growth advantage to transplanted tumor cells in vivo and to cells grown in vitro at high density. Frat1 might exert its activity by impairing the kinase activity of Gsk3beta, which is involved in the degradation of beta-catenin. Pim genes appear to act in tumor initiation and show strong synergism with myc in lymphomagenesis. Overexpression of Pim1 can also overcome some of the proliferative defects caused by defective interleukin signaling supporting a role of Pim1 in cell proliferation. We have applied proviral tagging in compound mutant Emu-myc/Pim1-/-/Pim2-/- mice to identify genes that can complement for the loss of Pim1 and Pim2 and, therefore, are able to synergize with c-myc in lymphomagenesis. A number of new as well as known genes have been found by this "complementation tagging." The latter included c-kit, Tp12, and cyclin D2, suggesting that Pim kinases might act upstream of or parallel to these known proto-oncogenes.
authors: Division of Molecular Genetics, The Netherlands Cancer Institute and Centre of Biomedical Genetics, Amsterdam.
authors: A
authors: A
authors: Berns
authors: H
authors: H
authors: Mikkers
authors: P
authors: P
authors: Krimpenfort
authors: J
authors: J
authors: Allen
authors: B
authors: B
authors: Scheijen
authors: J
authors: J
authors: Jonkers
mesh_terms: D000818:Animals; D018450:Disease Progression; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics*; D009857:Oncogenes