M. Gaire et al., PROTEIN-KINASE-C ISOTYPES REQUIRED FOR PHORBOL-ESTER INDUCTION OF STROMELYSIN-1 IN RAT FIBROBLASTS, Molecular carcinogenesis, 15(2), 1996, pp. 124-133
The phorbol-ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate
(TPA) is a potent inducer of the metalloproteinase stromelysin in fibr
oblasts in vivo and in several cultured cell lines. Rat-1 and Rat-2 fi
broblasts, however, do not respond to TPA stimulation by induction of
stromelysin gene activity, although collagenase promoter-mediated acti
vity is induced threefold by TPA treatment in these cells. We determin
ed that rat fibroblasts expressed protein kinase C (PKC) alpha, PKC de
lta, PKC epsilon, and PKC zeta but neither the mRNA nor the protein fo
r PKC beta. When Rat-2 fibroblasts were stably transfected with an exp
ression vector producing PKC beta, however, TPA treatment of these var
iants resulted in a 3.1-fold induction of stromelysin promoter-mediate
d luciferase activity compared with a 1.3-fold induction in parental R
at-2 cells (P < 0.002). Transient transfection of PKC epsilon produced
a small but significant increase in TPA-stimulation of both stromelys
in- and collagenase-mediated gene expression. These results suggest th
at there are PKC isotype-specific signaling pathways that can differen
tially regulate matrix metalloproteinase gene expression. (C) 1996 Wil
ey-Liss, Inc.