1. ¹Physiological Chemistry I, Theodor-Boveri-Institute, Biocenter of the University of Wuerzburg, Wuerzburg 97074, Germany
2. ²Institute of Molecular Biology and Tumor Research (IMT), University of Marburg, Marburg, Germany
3. ³Children's Hospital, Department of Molecular Genetics, University of Mainz, Mainz, Germany
4. ⁴Children's Hospital, Department of Paediatric Oncology and Haematology, University of the Saarland, Saarland, Germany

Correspondence: M Gessler, E-mail: gessler@biozentrum.uni-wuerzburg.de

Received 10 December 2004; Revised 23 February 2005; Accepted 1 April 2005; Published online 9 May 2005.

Abstract

Wilms tumor is one of the most frequent neoplasias in children. Our previous microarray screening in a large series of Wilms tumors revealed several candidate genes that are deregulated in advanced tumors and are part of the retinoic acid signaling pathway. To investigate whether retinoic acid could be employed as a novel therapeutic agent in these tumors, we treated cultured Wilms tumor cells with different concentrations of all-trans retinoic acid (ATRA) and assessed gene expression changes by real-time RT–PCR as well as microarray analysis. Several genes like RARRES1, RARRES3, CTGF, CKS2, CCNA2, IGFBP3, UBE2C, CCL2 or ITM2B that were previously found to be deregulated in advanced tumors exhibited opposite expression changes after ATRA treatment. In addition to enhanced retinoid signaling, the transforming growth factor-beta (TGF) pathway was strongly activated by ATRA treatment of Wilms tumor cells. Both the retinoic acid and the TGF pathway mediate inhibition of cell growth. These findings represent the first molecular evidence of a potential benefit from ATRA treatment in Wilms tumors.