S. Desouza et al., A NOVEL NERVE GROWTH FACTOR-RESPONSIVE ELEMENT IN THE STROMELYSIN-1 (TRANSIN) GENE THAT IS NECESSARY AND SUFFICIENT FOR GENE-EXPRESSION IN PC12 CELLS, The Journal of biological chemistry, 270(16), 1995, pp. 9106-9114
Stromelysin-1 (ST-1) is an extracellular matrix metalloproteinase whos
e expression is transcriptionally regulated by nerve growth factor (NG
F) in the PC12 rat pheochromocytoma cell line. In this paper, we defin
e sequences in the proximal ST-1 promoter that contain a novel NGF-res
ponsive element(s). We show that this cis-acting promoter element can
bind nuclear proteins from both untreated and NGF-treated PC12 cells i
n a specific and saturable manner and is sufficient to confer NGF-indu
cibility to a heterologous promoter. At least a portion of this NGF-re
sponsive element lies within a 12-base pair region between positions -
241 and -229 of the ST-1 promoter and bears no sequence homology to ot
her known transcriptional elements. In contrast to what has been repor
ted for fibroblasts, an AP1 site centered around position -68 does not
seem to be involved in the growth factor regulation of ST-1 in PC12 c
ells. These results suggest that the NGF regulation of ST-1 gene expre
ssion involves different promoter elements, and possibly different tra
nscription factors, from that described for ST-1 induction by other gr
owth factors.