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

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

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
Externally publishedYes

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Lung Neoplasms
Neoplasms
Oncogenes
Transgenic Mice
Modifier Genes
bcl-2 Genes
DNA Nucleotidylexotransferase
Proliferating Cell Nuclear Antigen
S Phase
Adenoma
Breeding
Cell Proliferation
Staining and Labeling
Phenotype
Lung
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fedorov, L., 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.

Bcl-2 determines susceptibility to induction of lung cancer by oncogenic CRaf. / Fedorov, Lev; Tyrsin, Oleg Yu; Papadopoulos, Thomas; Camarero, Guadalupe; Götz, Rudolf; Rapp, Ulf R.

In: Cancer Research, Vol. 62, No. 21, 01.11.2002, p. 6297-6303.

Research output: Contribution to journalArticle

Fedorov, L, Tyrsin, OY, Papadopoulos, T, Camarero, G, Götz, R & Rapp, UR 2002, 'Bcl-2 determines susceptibility to induction of lung cancer by oncogenic CRaf', Cancer Research, vol. 62, no. 21, pp. 6297-6303.
Fedorov L, Tyrsin OY, Papadopoulos T, Camarero G, Götz R, Rapp UR. Bcl-2 determines susceptibility to induction of lung cancer by oncogenic CRaf. Cancer Research. 2002 Nov 1;62(21):6297-6303.
Fedorov, Lev ; Tyrsin, Oleg Yu ; Papadopoulos, Thomas ; Camarero, Guadalupe ; Götz, Rudolf ; Rapp, Ulf R. / Bcl-2 determines susceptibility to induction of lung cancer by oncogenic CRaf. In: Cancer Research. 2002 ; Vol. 62, No. 21. pp. 6297-6303.
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