Bcl-2 determines susceptibility to induction of lung cancer by oncogenic CRaf.
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.
Fedorov
Lev M
LM
Institut für Medizinische Strahlenkunde und Zellforschung, Bayerische Julius-Maximilians-Universität, D-97078 Würzburg, Germany.
Tyrsin
Oleg Yu
OY
Papadopoulos
Thomas
T
Camarero
Guadalupe
G
Götz
Rudolf
R
Rapp
Ulf R
UR
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*
D019908:Proto-Oncogene Proteins c-raf