The role of sLZIP in transcriptional regulation of c-Jun and involvement in migration and invasion of cervical cancer cells.
OBJECTIVE
Matrix metalloproteinase-9 (MMP-9) plays an important role in tumor invasion and metastasis through the breakdown of extracellular matrix. The c-Jun protein, a major component of the AP-1 transcription factor, is elevated in various cancers. Small leucine zipper protein (sLZIP) is a member of the leucine zipper transcription factor family. Although sLZIP is known to be involved in cancer cell migration and invasion, its biological roles in cancer development and the cellular target genes are not fully understood. In this study, we investigated the role of sLZIP in c-Jun expression, and their effects on expression of MMP-9 and migration of cervical cancer cells.


RESULTS
sLZIP up-regulates transcription of c-Jun by binding directly to the CRE region in the c-Jun promoter. Elevated c-Jun due to sLZIP leads to activation of MMP-9 transcription by interaction with the AP-1 binding site in the MMP-9 promoter. c-Jun siRNA repressed migration and invasion of cervical cancer cells, whereas sLZIP recovered migration and invasion of cells transfected with c-Jun siRNA. Immunohistochemical analysis results revealed a significant correlation between the expressions of sLZIP and MMP-9 in clinical cervical specimens.


CONCLUSIONS
These results indicate that sLZIP plays a role in expression of c-Jun, and migration and invasion of cervical cancer cells via regulation of MMP-9 transcription.
Division of Life Sciences, Korea University, Seoul, South Korea.
Eunsoo
E
Park
Hyereen
H
Kang
Jeonghan
J
Kim
Jesang
J
Ko
D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*
C107941:CREB3 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D020780:Matrix Metalloproteinase 9