Journal article
Bax accelerates tumorigenesis in p53-deficient mice
Cancer research (Chicago, Ill.), Vol.61(2), pp.659-665
2001
PMID: 11212265
Abstract
Bax is a Bcl-2 family member that promotes apoptosis and counters the protective effect of Bcl-2. Bax is a downstream effector of p53-induced apoptosis and is transcriptionally regulated by p53. Moreover, the introduction of Bax deficiency accelerates the onset of tumors in transgenic mice expressing truncated large T antigen. These results implicate Bax as a tumor suppressor. Consequently, we asked whether the levels of Bax expression would influence tumor development by comparing Bax-deficient and Bax transgenic mice in the presence or absence of p53. We found that Bax-deficient mice did not display an increased incidence of spontaneous cancers when followed for > 1.5 years. In addition, Bax-deficiency did not further accelerate oncogenesis in mice also deficient in p53. We generated Lck(pr)-Bax transgenic mice to examine the effects of overexpressed BAX on T-cell development and tumorigenesis. Lck(pr)-Bax mice show increased apoptosis consistent with the pro-apoptotic function of Bax. The introduction of p53-deficiency did not interfere with BAX-induced apoptosis; this is consistent with BAX operating downstream or independent of p53. However, we found that Lck(pr)-Bax/p53-deficient mice have an increased incidence of T-cell lymphomas when compared with p53-deficient mice. The Lck(pr)-Bax transgenic mice have an increased percentage of cells in cycle. These findings extend previous work suggesting that Bcl-2 family proteins regulate proliferation as well as cell death. We conclude that BAX-induced proliferation is synergistic with a defect in apoptosis contributed by p53-deficiency. Thus, the dual roles of BAX can either accelerate or inhibit tumorigenesis depending on the genetic context.
Details
- Title: Subtitle
- Bax accelerates tumorigenesis in p53-deficient mice
- Creators
- C. Michael KNUDSON - Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52241, United StatesGeoffrey M JOHNSON - Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52241, United StatesYuan Lin - Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52241, United StatesStanley J KORSMEYER - Department of Pathology and Medicine, Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.61(2), pp.659-665
- Publisher
- American Association for Cancer Research; Philadelphia, PA
- PMID
- 11212265
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 2001
- Academic Unit
- Pathology; Radiation Oncology
- Record Identifier
- 9984047869702771
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