Regulation of urokinase-type plasminogen activator expression by the v-mos oncogene.
We undertook a study to determine if the serine-threonine kinase-encoding v-mos oncogene regulated the expression of the urokinase-type plasminogen activator. An expression vector encoding v-mos, but not a kinase-inactive mutant, stimulated urokinase promoter activity in CAT assays employing a squamous cell carcinoma cell line. The induction of urokinase promoter activity by v-mos was mediated, in part, via an increased AP-1 activity since (a) mutation of 2 AP-1 binding sites (at -1967 and -1885), or the co-expression of a transactivation domain-lacking c-jun mutant reduced the induction of the urokinase promoter by v-mos and (b) expression of v-mos increased the activity of a CAT reporter driven by three AP-1 tandem repeats. The stimulation of the urokinase promoter by v-mos was partially countered by co-expression of an ERK1/ERK2-inactivating phosphatase. Western blotting and zymographic analysis indicated that v-mos-transformed NIH3T3 cells (MSV NIH-3T3) secreted more urokinase compared with NIH3T3 cells and this was associated with a higher level of activated ERK1 and ERK2. Expression of a catalytically-inactive MAPKK mutant reduced the activity of a urokinase promoter-driven CAT reporter in the MSV NIH-3T3 cells. In conclusion, the data herein indicate that urokinase expression is regulated by v-mos through a MAPKK-dependent signaling pathway.
Lengye
E
E
Department of Tumor Biology, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Singh
B
B
Gum
R
R
Nerlov
C
C
Sabichi
A
A
Birrer
M
M
Boyd
D
D
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases; D008969:Molecular Sequence Data; D017232:Oncogene Proteins v-mos / Q000235:genetics*; D009857:Oncogenes; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D017232:Oncogene Proteins v-mos; D018808:Transcription Factor AP-1; D011494:Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D014568:Urokinase-Type Plasminogen Activator