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 NIH3T3 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 down-regulation of Bcl-2.
Molecular Medicine, Northwest Hospital, Seattle, WA 98125, USA. rphuang@nwlink.com
R P
RP
Huang
Y
Y
Fan
A
A
Peng
Z L
ZL
Zeng
J C
JC
Reed
E D
ED
Adamson
A L
AL
Boynton
D015153:Blotting, Western; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D051766:Early Growth Response Protein 1; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017874:Immediate-Early Proteins; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D015342:DNA Probes; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors