Egr-2 is a tumour repressive gene (165.1)

Abstract

Abstract EGR-2, a zinc finger domain containing transcription factor, plays an important role in the development of both centre never system and T lymphocytes. However, the mechanism of action is unknown. To investigate Egr-2 function in lymphocytes, we have developed lymphocyte specific Egr-2 KO (Knockout) and Tg (Transgenic) mice. In the absence of Egr-2, the homeostasis of T cells is disregulated with hyper-proliferation of effector phenotype cells. In addition to the increased effector phenotype lymphocytes, the development of spontanouse B and T cell lymphoma in Egr-2 KO mice has been found at later age. More than 30% Egr-2 KO mice aged more than 12-months developed either T or B cell lymphoma. Oncogene-database (Oncomine gene expression database) search showed that the expression of Egr-2 is either suppressed or deleted in haematopoietic tumours. To explore anti-tumour function, Egr-2 was transfected into HKE 293 and mouse melanoma B16 cell lines, respectively. The transfected cells exhibited small cell body and stopped cell division. In the undergoing mechanism study, we found that 1), The expression of p53 was increased in lymphocytes from Egr-2 Tg mice and p53 was phosphorylated in Egr-2 transfected HKE293 cells.2), Egr-2 binds to c-Jun, the key components of AP-1; 3), Egr-2 strongly inhibited STATs transcriptional activity. Our results suggest that tumour suppressive role of Egr-2 involved in multple cell signalling pathways.