Ectopic expression of E47 or E12 promotes the death of E2A-deficient lymphomas

Mice with null mutations in the E2A gene are highly susceptible to the spon taneous development of thymic lymphomas. To understand better how E2A defic iency may contribute to lymphomagenesis, we have observed the consequences of enforced expression of the E2A gene products E12 and E47 in cell lines d erived from lymphomas that arose spontaneously in E2A-deficient mice. E2A-e xpressing cells are steadily eliminated from lymphoma cultures into which E 47 or E12 was introduced. The mechanism underlying the loss of E2A-expressi ng cells does not involve an arrest in cell-cycle progression. Rather, the E2A proteins activate a programmed cell death pathway in these lymphomas. T his E2A-mediated cell death appears to be preceded by a loss of mitochondri al transmembrane potential. These data provide direct evidence that E2A gen e products can act as tumor suppressors.