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Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9324-9. Epub 2003 Jul 22.

Bad-deficient mice develop diffuse large B cell lymphoma.

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  • 1Howard Hughes Medical Institute and Department of Pathology, Harvard Medical School and Dana-Farber Cancer Institute, Boston, MA 02115, USA.

Abstract

The proapoptotic activity of the "BH3-only" molecule BAD can be differentially regulated by survival factor signaling. Bad-deficient mice lacking both BAD long and BAD short proteins proved viable, and most cell types appeared to develop normally. BAD did not exclusively account for cell death after withdrawal of survival factors, but it was an intermediate for epidermal growth factor- or insulin-like growth factor I-countered apoptosis, consistent with a "sensitizing" BH3-only molecule. Lymphocytes developed normally with no premalignant hyperplasia, but they displayed subtle abnormalities in proliferation and IgG production. Despite the minimal phenotype, Bad-deficient mice progressed, with aging, to diffuse large B cell lymphoma of germinal center origin. Exposure of Bad-null mice to sublethal gamma-irradiation resulted in an increased incidence of pre-T cell and pro-/pre-B cell lymphoblastic leukemia/lymphoma. Thus, proapoptotic BAD suppresses tumorigenesis in the lymphocyte lineage.

PMID:
12876200
[PubMed - indexed for MEDLINE]
PMCID:
PMC170917
Free PMC Article
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