Jensen, Mads Aaboe2; Birkenkamp-Demtröder, Karin8; Wiuf, Carsten9; Sørensen, Flemming Brandt3; Andersen, Thomas Thykjær2; Sauter, Guido7; Jensen, Klaus Møller-Ernst4; Andersen, Lars Dyrskjøt8; Ørntoft, Torben Falck8
1 Bioinformatics Research Centre (BiRC), Faculty of Science, Aarhus University, Aarhus University2 Department of clinical biochemistry, Faculty of Health Sciences, Aarhus University, Aarhus University3 The Department of Pathology, Faculty of Health Sciences, Aarhus University, Aarhus University4 The Department of Urology K, Faculty of Health Sciences, Aarhus University, Aarhus University5 Department of Clinical Medicine - Molekylær Medicinsk afdeling (MOMA), Department of Clinical Medicine, Health, Aarhus University6 Department of Clinical Medicine - Enhed for Bioinformatik, Department of Clinical Medicine, Health, Aarhus University7 Institutes for Pathology, University of Basel,8 Department of Clinical Medicine - Molekylær Medicinsk afdeling (MOMA), Department of Clinical Medicine, Health, Aarhus University9 Department of Clinical Medicine - Enhed for Bioinformatik, Department of Clinical Medicine, Health, Aarhus University
The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4-specific antibody, we found that the cancer cells expressed the SOX4 protein and, thus, did an evaluation of SOX4 protein expression in 2,360 bladder tumors using a tissue microarray with clinical annotation. We found a correlation (P < 0.05) between strong SOX4 expression and increased patient survival. When overexpressed in the bladder cell line HU609, SOX4 strongly impaired cell viability and promoted apoptosis. To characterize downstream target genes and SOX4-induced pathways, we used a time-course global expression study of the overexpressed SOX4. Analysis of the microarray data showed 130 novel SOX4-related genes, some involved in signal transduction (MAP2K5), angiogenesis (NRP2), and cell cycle arrest (PIK3R3) and others with unknown functions (CGI-62). Among the genes regulated by SOX4, 25 contained at least one SOX4-binding motif in the promoter sequence, suggesting a direct binding of SOX4. The gene set identified in vitro was analyzed in the clinical bladder material and a small subset of the genes showed a high correlation to SOX4 expression. The present data suggest a role of SOX4 in the bladder cancer disease.
Cancer Research, 2006, Vol 66, Issue (7), p. 3434-42