A NOVEL NERVE GROWTH FACTOR-RESPONSIVE ELEMENT IN THE STROMELYSIN-1 (TRANSIN) GENE THAT IS NECESSARY AND SUFFICIENT FOR GENE-EXPRESSION IN PC12 CELLS

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.