Lymphoma development in Bax transgenic mice is inhibited by Bcl-2 and associated with chromosomal instability

J J Luke; C I Van De Wetering; C M Knudson

doi:10.1038/sj.cdd.4401233

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Lymphoma development in Bax transgenic mice is inhibited by Bcl-2 and associated with chromosomal instability

Journal article

Open access

Peer reviewed

Lymphoma development in Bax transgenic mice is inhibited by Bcl-2 and associated with chromosomal instability

J J Luke, C I Van De Wetering and C M Knudson

Cell death and differentiation, Vol.10(6), pp.740-748

06/2003

DOI: 10.1038/sj.cdd.4401233

PMID: 12761582

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https://doi.org/10.1038/sj.cdd.4401233View

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Abstract

Bax is a Bcl-2 family member that promotes apoptosis but has paradoxical effects on lymphoma development in p53-deficient mice. To better understand the mechanism of Bax-induced lymphoma development, the effect of Bax levels, p53 status and Bcl-2 coexpression on lymphoma development were determined. In addition, DNA content and cytogenetics were performed on young (premalignant) Lck-Bax mice as measures of genetic instability. Bax promoted lymphoma development in p53-deficient mice in a dose-dependent manner. Bax expression also led to lymphoma development in both p53 +/- and +/+ animals. Ploidy analysis in mice prior to the onset of overt thymic lymphomas demonstrated that Lck-Bax transgenic mice were more likely to be aneuploid and demonstrate increased chromosome instability. With tumor progression, aneuploidy increased and Bax expression was maintained. Importantly, coexpression of Bcl-2 delayed lymphoma development in Lck-Bax transgenic mice. These data support a model in which increased sensitivity to apoptosis leads directly to chromosome instability in developing T cells and may explain a number of paradoxical observations regarding Bcl-2 family members and the regulation of cancer.

Proto-Oncogene Proteins - metabolism

Genetic Predisposition to Disease

Lymphoma - genetics

Aneuploidy

Apoptosis - genetics

Mice, Transgenic

Proto-Oncogene Proteins - genetics

bcl-2-Associated X Protein

Tumor Suppressor Protein p53 - deficiency

Cell Transformation, Neoplastic - metabolism

Tumor Suppressor Protein p53 - genetics

Chromosomal Instability - genetics

Proto-Oncogene Proteins c-bcl-2 - metabolism

Animals

Cell Transformation, Neoplastic - genetics

Lymphoma - enzymology

Mice

Proto-Oncogene Proteins c-bcl-2 - genetics

Gene Expression Regulation, Neoplastic - genetics

Disease Models, Animal

Details

Title: Subtitle: Lymphoma development in Bax transgenic mice is inhibited by Bcl-2 and associated with chromosomal instability
Creators: J J Luke - Department of Pathology, The University of Iowa Roy J. and Lucille P. Carver College of Medicine, Iowa City 52242, USA
C I Van De Wetering
C M Knudson
Resource Type: Journal article
Publication Details: Cell death and differentiation, Vol.10(6), pp.740-748
Publisher: England
DOI: 10.1038/sj.cdd.4401233
PMID: 12761582
ISSN: 1350-9047
eISSN: 1476-5403
Language: English
Date published: 06/2003
Academic Unit: Pathology; Radiation Oncology
Record Identifier: 9984047760702771

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