Identification of IGFBP-6 as a significantly downregulated gene by beta-catenin in desmoid tumors.
Desmoid tumors (aggressive fibromatosis) are locally invasive soft tissue tumors in which beta-catenin-mediated TCF-3-dependent transcription is activated. To provide more insight into the pathophysiology of these tumors, expression profiles were generated using oligonucleotide arrays (Affymetrix). In total, 69 differentially expressed genes were identified in desmoids compared to normal fibroblasts (fascia) from the same patients. The differential expression of a selection of genes was confirmed using RT-PCR and Northern blotting. We further evaluated the insulin-like growth factor-binding protein 6 (IGFBP-6), a gene that was consistently downregulated in all desmoids tested. Promotor studies and electromobility shift assays revealed two functional beta-catenin/TCF-responsive elements in the human IGFBP-6 promoter. These findings suggest that IGFBP-6 is directly downregulated by the beta-catenin/TCF complex in desmoid tumors, and imply a role for the IGF axis in the proliferation of desmoid tumors.
Denys
Hannelore
H
Center for Human Genetics, University of Leuven, Leuven B-3000, Belgium.
Jadidizadeh
Ali
A
Amini Nik
Saeid
S
Van Dam
Kim
K
Aerts
Stein
S
Alman
Benjamin A
BA
Cassiman
Jean-Jacques
JJ
Tejpar
Sabine
S
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D016466:CHO Cells; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000502:physiology*; D017931:DNA Primers; D015536:Down-Regulation / Q000502:physiology*; D005350:Fibroma / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000502:physiology*; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D003598:Cytoskeletal Proteins; D017931:DNA Primers; D018976:Insulin-Like Growth Factor Binding Protein 6; D015534:Trans-Activators; D051176:beta Catenin