Hipk2 cooperates with p53 to suppress γ-ray radiation-induced mouse thymic lymphoma

A genome-wide screen for genetic alterations in radiation-induced thymic lymphomas generated from p53 +/− and p53 −/− mice showed frequent loss of heterozygosity (LOH) on chromosome 6. Fine mapping of these LOH regions revealed three non-overlapping regions, one of which was refined to a 0.2 Mb inte...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Oncogene Jg. 31; H. 9; S. 1176 - 1180
Hauptverfasser: Mao, J-H, Wu, D, Kim, I-J, Kang, H C, Wei, G, Climent, J, Kumar, A, Pelorosso, F G, DelRosario, R, Huang, E J, Balmain, A
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 01.03.2012
Nature Publishing Group
Schlagworte:
Animals
Apoptosis
BASIC BIOLOGICAL SCIENCES
Biochemistry & Molecular Biology
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Biology
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Cell Transformation, Neoplastic - radiation effects
chromosome 6
Chromosomes, Mammalian
gamma Radiation
Gamma rays
Gamma Rays - adverse effects
Gene Expression Regulation, Neoplastic
Gene mapping
Genetic aspects
Genetics & Heredity
Health aspects
HIPK2 protein
Human Genetics
Internal Medicine
Loss of Heterozygosity
Lymphoma
Lymphoma - genetics
Lymphoma - metabolism
Lymphomas
Medicine
Medicine & Public Health
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasms, Radiation-Induced - genetics
Neoplasms, Radiation-Induced - metabolism
Oncology
Original
original-article
p53 protein
Peptide mapping
Physiological aspects
Protein Binding
Protein kinase
Protein kinases
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Risk factors
Thymus
Thymus Neoplasms - genetics
Thymus Neoplasms - metabolism
Tumor proteins
Tumor suppressor genes
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Tumors
United States
radiation
tumorigenesis
p53
ISSN:0950-9232, 1476-5594, 1476-5594
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:A genome-wide screen for genetic alterations in radiation-induced thymic lymphomas generated from p53 +/− and p53 −/− mice showed frequent loss of heterozygosity (LOH) on chromosome 6. Fine mapping of these LOH regions revealed three non-overlapping regions, one of which was refined to a 0.2 Mb interval that contained only the gene encoding homeobox-interacting protein kinase 2 ( Hipk2 ). More than 30% of radiation-induced tumors from both p53 +/− and p53 −/− mice showed heterozygous loss of one Hipk2 allele. Mice carrying a single inactive allele of Hipk2 in the germline were susceptible to induction of tumors by γ-radiation, but most tumors retained and expressed the wild-type allele, suggesting that Hipk2 is a haploinsufficient tumor suppressor gene for mouse lymphoma development. Heterozygous loss of both Hipk2 and p53 confers strong sensitization to radiation-induced lymphoma. We conclude that Hipk2 is a haploinsufficient lymphoma suppressor gene.
Bibliographie:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ObjectType-Article-1
ObjectType-Feature-2
AC02-05CH11231; FG02-03ER63630
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
ISSN:0950-9232
1476-5594
1476-5594
DOI:10.1038/onc.2011.306