1. ¹Center for Human Genetics, University of Leuven, Leuven B-3000, Belgium
2. ²Department of Electrical Engineering, University of Leuven, Leuven B-3001, Belgium
3. ³The Program in Developmental Biology, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada M5G1X8

Correspondence: S Tejpar, Center for Human Genetics, University of Leuven, Campus Gasthuisberg, Herestraat 49, Leuven B-3000, Belgium. E-mail: Sabine.Tejpar@med.kuleuven.ac.be

Received 11 May 2003; Revised 19 August 2003; Accepted 28 August 2003.

Abstract

Desmoid tumors (aggressive fibromatosis) are locally invasive soft tissue tumors in which -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 -catenin/TCF-responsive elements in the human IGFBP-6 promoter. These findings suggest that IGFBP-6 is directly downregulated by the -catenin/TCF complex in desmoid tumors, and imply a role for the IGF axis in the proliferation of desmoid tumors.