v-jun oncogene suppresses both phorbol ester-induced cell invasion and stromelysin gene expression in a mouse papilloma cell line.
The viral jun (v-jun) oncogene encodes a transcription factor that can participate in the transactivation of genes through the AP-1 complex. Evidence indicates that the ability of v-jun to transform cells and stimulate transcription depends on the cell type. We have asked whether expression of the v-jun gene in benign tumor forming mouse keratinocytes that already express an activated c-rasHa oncogene would cause malignant progression. Our results showed that the v-jun transfection did not result in malignant progression; instead, we made the unexpected observation that the ability of these cells to invade reconstituted basement membrane matrix (in vitro) in response to the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, was suppressed. This phenomenon could, in part, be explained by the suppression of the induction by phorbol ester of expression of the metalloproteinase, stromelysin (transin). Of interest was the finding that 12-O-tetradecanoylphorbol-13-acetate induction of other cellular genes known to be regulated by AP-1 was not inhibited in the benign tumor cells expressing v-jun.
Tsang
T C
TC
Department of Radiation Oncology, College of Medicine, University of Arizona, Tucson 85724.
Chu
Y W
YW
Powell
M B
MB
Kittelson
J
J
Meade-Tollin
L
L
Hendrix
M J
MJ
Bowden
G T
GT
D000818:Animals; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016758:Genes, jun; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D010212:Papilloma / Q000378:metabolism / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D013755:Tetradecanoylphorbol Acetate