A role for AP-1 in matrix metalloproteinase production and invadopodia formation of v-Crk-transformed cells.
Both MMP-2 and MMP-9 play critical roles in tumor invasion, but their productions are differentially controlled. While the promoter region of MMP-9 has the conserved proximal AP-1 binding site, that of the MMP-2 has a noncanonical AP-1 site. To assess the role of AP-1 function, we examined the effects of dominant-negative Fos (DeltaFos), BATF and siRNA against c-Jun on MMP production in v-Crk-transformed cells which have augmented production of MMP-2 and MMP-9. Suppression of AP-1 dependent transcription by conditional expression of dominant-negative Fos (DeltaFos) and BATF substantially inhibited not only MMP-9 production but also MMP-2 production. The ChIP analysis showed the direct association of AP-1 and MMP-2 promoter region. In addition, silencing of c-Jun expression by siRNA transfection suppressed MMP-2 and MMP-9 production and in vitro invasiveness. Furthermore, the invadopodia formation of v-Crk-transformed cells could be suppressed by BATF expression or c-Jun siRNA treatment. Taken together, AP-1 appears to play a critical role in the production of MMP-2 and MMP-9 and invadopodia formation of v-Crk-transformed cells.
Hasegawa
Hitoki
H
Division of Cancer Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Senga
Takeshi
T
Ito
Satoko
S
Iwamoto
Takashi
T
Hamaguchi
Michinari
M
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002461:Cell Line, Transformed; D017353:Gene Deletion; D005786:Gene Expression Regulation; D015151:Immunoblotting; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D050736:Oncogene Protein v-crk / Q000235:genetics*; D016761:Oncogene Proteins v-fos / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D050736:Oncogene Protein v-crk; D016761:Oncogene Proteins v-fos; D018808:Transcription Factor AP-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9