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 t he proliferation of v-sis transformed N1H3T3 cells and also a number o f human tumor cells. Here, we investigate the possible mechanisms resp onsible for this function. We show that transfected Egr-1 in human fib rosarcoma cells HT1080 leads to down-regulation of Bcl-2. Transient CA T transfection assays reveal that expression of Egr-1 suppresses Bcl-2 promoter activity in a dose-dependent manner. Furthermore, overexpres sion of Bcl-2 in Egr-1-expressing HT1080 cells enhanced cell prolifera tion in monolayer culture and increased anchorage-independent growth. Our results suggest that suppression of tumor cell proliferation by Eg r-1 may be at least partially mediated through the downregulation of B cl-2. (C) 1998 Wiley-Liss, Inc.