Using a cDNA gene expression array system, we identified fra-1 as a novel t
arget molecule for retinoid action in the human pancreatic carcinoma cell l
ine Dan-G. Retinoid treatment resulted in a significant and time-dependent
induction of the fra-1 expression on the post-transcriptional level. Supers
hift assays revealed that fra-1 participates in the activator protein 1 com
plex together with c-fos, c-jun and junB, Transient transfection experiment
s using a reporter plasmid containing an activator protein site upstream of
the CAT reporter gene revealed that the phorbolester-induced CAT activity,
vas suppressed by retinoids, Since fra-1 lacks a transactivation function,
we therefore suggest that the retinoid-mediated induction of fra-1 might fu
nction as a negative regulator of the activator protein 1 activity in human
pancreatic carcinoma cells. (C) 1999 Federation of European Biochemical So
cieties.