Bcl-2 determines susceptibility to induction of lung cancer by oncogenic CRaf

Lev M. Fedorov, Oleg Yu Tyrsin, Thomas Papadopoulos, Guadalupe Camarero, Rudolf Götz, Ulf R. Rapp

    Research output: Contribution to journalArticle

    25 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)6297-6303
    Number of pages7
    JournalCancer Research
    Volume62
    Issue number21
    StatePublished - Nov 1 2002

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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  • Cite this

    Fedorov, L. M., Tyrsin, O. Y., Papadopoulos, T., Camarero, G., Götz, R., & Rapp, U. R. (2002). Bcl-2 determines susceptibility to induction of lung cancer by oncogenic CRaf. Cancer Research, 62(21), 6297-6303.