Suppression Of Human Fibrosarcoma Cell Growth By Transcription Factor, Egr-1, Involves Down-Regulation Of Bcl-2

Previously, we showed that the transcription factor Egr-1 suppressed the proliferation of v-sis transformed N1H3T3 cells and also a number of human tumor cells. Here, we investigate the possible mechanisms responsible for this function. We show that transfected Egr-1 in human fibrosarcoma cells HT1080 leads to down-regulation of Bcl-2. Transient CAT transfection assays reveal that expression of Egr-1 suppresses Bcl-2 promoter activity in a dose-dependent manner. Furthermore, overexpression of Bcl-2 in Egr-1-expressing HT1080 cells enhanced cell proliferation in monolayer culture and increased anchorage-independent growth. Our results suggest that suppression of tumor cell proliferation by Egr-1 may be at least partially mediated through the downregulation of Bcl-2. (C) 1998 Wiley-Liss, Inc.