Tumor induction and tissue atrophy in mice lacking E2F-1.
The retinoblastoma tumor suppressor protein (pRB) is a transcriptional repressor that regulates gene expression by physically associating with transcription factors such as E2F family members. Although pRB and its upstream regulators are commonly mutated in human cancer, the physiological role of the pRB-E2F pathway is unknown. To address the function of E2F-1 and pRB/E2F-1 complexes in vivo, we have produced mice homozygous for a nonfunctional E2F-1 allele. Mice lacking E2F-1 are viable and fertile, yet experience testicular atrophy and exocrine gland dysplasia. Surprisingly, mice lacking E2F-1 develop a broad and unusual spectrum of tumors. Although overexpression of E2F-1 in tissue culture cells can stimulate cell proliferation and be oncogenic, loss of E2F-1 in mice results in tumorigenesis, demonstrating that E2F-1 also functions as a tumor suppressor.
Yamasaki
L
L
Massachusetts General Hospital Cancer Center, Charlestown 02129, USA.
Jacks
T
T
Bronson
R
R
Goillot
E
E
Harlow
E
E
Dyson
N J
NJ
D000818:Animals; D001284:Atrophy; D001483:Base Sequence; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics; D002678:Chimera; D004268:DNA-Binding Proteins / Q000235:genetics; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005088:Exocrine Glands / Q000473:pathology / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D008175:Lung Neoplasms / Q000235:genetics; D008223:Lymphoma / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D011995:Recombination, Genetic / Q000502:physiology; D056465:Retinoblastoma-Binding Protein 1; D012513:Sarcoma, Experimental / Q000235:genetics; D013737:Testis / Q000473:pathology* / Q000502:physiology; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics*
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors