Abstract
Mice with null mutations in the E2A gene are highly susceptible to the spontaneous development of thymic lymphomas. To understand better how E2A deficiency may contribute to lymphomagenesis, we have observed the consequences of enforced expression of the E2A gene products E12 and E47 in cell lines derived from lymphomas that arose spontaneously in E2A-deficient mice. E2A-expressing cells are steadily eliminated from lymphoma cultures into which E47 or E12 was introduced. The mechanism underlying the loss of E2A-expressing cells does not involve an arrest in cell-cycle progression. Rather, the E2A proteins activate a programmed cell death pathway in these lymphomas. This E2A-mediated cell death appears to be preceded by a loss of mitochondrial transmembrane potential. These data provide direct evidence that E2A gene products can act as tumor suppressors.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenovirus E2 Proteins / deficiency
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Adenovirus E2 Proteins / genetics*
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Animals
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Cell Cycle
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Cell Death
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Helix-Loop-Helix Motifs
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Humans
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Intracellular Membranes / physiology
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Lymphoma / genetics*
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Lymphoma / pathology
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Lymphoma / physiopathology
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Lymphoma, T-Cell / genetics
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Membrane Potentials / physiology
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Mice
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Mice, Knockout
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Mitochondria / physiology
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Recombinant Proteins / metabolism
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TCF Transcription Factors
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Thymoma / genetics*
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Thymoma / pathology
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Thymoma / physiopathology
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Thymus Neoplasms / genetics*
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Thymus Neoplasms / pathology
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Thymus Neoplasms / physiopathology
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Transcription Factor 7-Like 1 Protein
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Transcription Factors / metabolism
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Transfection
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Tumor Cells, Cultured
Substances
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Adenovirus E2 Proteins
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DNA-Binding Proteins
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Recombinant Proteins
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TCF Transcription Factors
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TCF7L1 protein, human
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Tcf7l1 protein, mouse
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Transcription Factor 7-Like 1 Protein
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Transcription Factors