title: Bcl-2 determines susceptibility to induction of lung cancer by oncogenic CRaf.
abstract: The efficiency of tumor induction by oncogenes is influenced by modifier genes that determine individual susceptibility. We have used a transgenic mouse model to examine the role of a candidate susceptibility gene, bcl-2, for development of Raf oncogene-induced lung adenomas. Loss of bcl-2 greatly retarded tumor development without affecting tumor phenotype. Tumor tissues from bcl-2 positive and negative mice were compared for the fraction of S phase cells by staining for proliferating cell nuclear antigen and for the fraction of apoptotic cells by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. The data indicate that the increased tumor latency in the absence of bcl-2 results primarily from an increased apoptotic rate but also involves a decrease in tumor cell proliferation. Both effects can be rescued by breeding with H2K-bcl-2 transgenic mice demonstrating that loss of bcl-2 was the major genetic factor determining tumor resistance. These findings suggest that bcl-2 is a major susceptibility gene for development of lung cancer in mice and perhaps in humans.
authors.affiliation: Institut für Medizinische Strahlenkunde und Zellforschung, Bayerische Julius-Maximilians-Universität, D-97078 Würzburg, Germany.
authors.forename: Lev M
authors.initials: LM
authors.lastname: Fedorov
authors.forename: Oleg Yu
authors.initials: OY
authors.lastname: Tyrsin
authors.forename: Thomas
authors.initials: T
authors.lastname: Papadopoulos
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Camarero
authors.forename: Rudolf
authors.initials: R
authors.lastname: Götz
authors.forename: Ulf R
authors.initials: UR
authors.lastname: Rapp
mesh_terms: D000818:Animals; D019254:Genes, bcl-2 / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009857:Oncogenes / Q000502:physiology; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*
chemical_list: D019908:Proto-Oncogene Proteins c-raf