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Protein kinase C isotypes required for phorbol‐ester induction of stromelysin‐1 in rat fibroblasts
Author(s) -
Gaire Mireille,
Barro Claire D.,
Kerr Lawrence D.,
Carlisle Frederick,
Matrisian Lynn M.
Publication year - 1996
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199602)15:2<124::aid-mc5>3.0.co;2-j
Subject(s) - biology , phorbol ester , protein kinase c , protein kinase a , phorbol , microbiology and biotechnology , biochemistry , kinase
The phorbol‐ester tumor promoter 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA) is a potent inducer of the metalloproteinase stromelysin in fibroblasts in vivo and in several cultured cell lines. Rat‐1 and Rat‐2 fibroblasts, however, do not respond to TPA stimulation by induction of stromelysin gene activity, although collagenase promoter‐mediated activity is induced threefold by TPA treatment in these cells. We determined that rat fibroblasts expressed protein kinase C (PKC) α, PKCδ, PKCϵ, and PKCζ but neither the mRNA nor the protein for PKCβ. When Rat‐2 fibroblasts were stably transfected with an expression vector producing PKCβ, however, TPA treatment of these variants resulted in a 3.1‐fold induction of stromelysin promoter‐mediated luciferase activity compared with a 1.3‐fold induction in parental Rat‐2 cells ( P < 0.002). Transient transfection of PKCϵ produced a small but significant increase in TPA‐stimulation of both stromelysin‐ and collagenase‐mediated gene expression. These results suggest that there are PKC isotype‐specific signaling pathways that can differentially regulate matrix metalloproteinase gene expression. © 1996 Wiley‐Liss, Inc.