| First Author | Fedorov LM | Year | 2002 |
| Journal | Cancer Res | Volume | 62 |
| Issue | 21 | Pages | 6297-303 |
| PubMed ID | 12414660 | Mgi Jnum | J:79696 |
| Mgi Id | MGI:2388790 | Citation | Fedorov LM, et al. (2002) Bcl-2 Determines Susceptibility to Induction of Lung Cancer by Oncogenic CRaf. Cancer Res 62(21):6297-303 |
| abstractText | 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. |
