Bad-deficient mice develop diffuse large B cell lymphoma.
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.
Ranger
Ann M
AM
Howard Hughes Medical Institute and Department of Pathology, Harvard Medical School and Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Zha
Jiping
J
Harada
Hisashi
H
Datta
Sandeep Robert
SR
Danial
Nika N
NN
Gilmore
Andrew P
AP
Kutok
Jeffery L
JL
Le Beau
Michelle M
MM
Greenberg
Michael E
ME
Korsmeyer
Stanley J
SJ
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D016923:Cell Death; D019070:Cell Lineage; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D005720:Gamma Rays; D007074:Immunoglobulin G; D007621:Karyotyping; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008957:Models, Genetic; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D014176:Protein Biosynthesis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D014158:Transcription, Genetic; D051025:bcl-Associated Death Protein
C494820:Bad protein, mouse; D002352:Carrier Proteins; D018076:DNA, Complementary; D007074:Immunoglobulin G; D051025:bcl-Associated Death Protein