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Publication : Midkine as a novel target gene for the Wilms' tumor suppressor gene (WT1).

First Author  Adachi Y Year  1996
Journal  Oncogene Volume  13
Issue  10 Pages  2197-203
PubMed ID  8950987 Mgi Jnum  J:37477
Mgi Id  MGI:84870 Citation  Adachi Y, et al. (1996) Midkine as a novel target gene for the Wilms' tumor suppressor gene (WT1). Oncogene 13(10):2197-203
abstractText  Midkine (MK) is a heparin-binding growth factor which is strongly expressed during the midgestation period of mouse embryogenesis. Wilms' tumor is an embryonal kidney malignancy in infants, and WT1 has been identified as its tumor suppressor gene. The high expression level of MK in all Wilms' tumor specimens so far examined and the presence of two WT1 elements (5'-GCGGGGGCG-3') in the human MK promoter region led us to examine the possible role of the WT1 gene product in the regulation of MK gene expression. A gel shift assay verified the complex formation between the WT1 gene product and WT1 consensus sequence of MK gene. DNase1 footprint analysis also demonstrated that the downstream WT1 element was protected from DNase1 cleavage by the addition of the WT1 protein. The human MK promoter fused with the chloramphenicol acetyltransferase gene (phMK2.3kCAT) was co-transfected with an effector plasmid containing the WT1 gene into several cell lines. Transient transfection assays showed suppression of the MK promoter by WT1 co-transfection in recipient cells; deletion of the WT1 binding site abolished the suppression. The evidence reported in this study indicates that MK gene is a newly identified WT1 target gene.
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