All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo.
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 (TGFbeta) pathway was strongly activated by ATRA treatment of Wilms tumor cells. Both the retinoic acid and the TGFbeta pathway mediate inhibition of cell growth. These findings represent the first molecular evidence of a potential benefit from ATRA treatment in Wilms tumors.
Zirn
Birgit
B
Physiological Chemistry I, Theodor-Boveri-Institute, Biocenter of the University of Wuerzburg, Wuerzburg 97074, Germany.
Samans
Birgit
B
Spangenberg
Christian
C
Graf
Norbert
N
Eilers
Martin
M
Gessler
Manfred
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000502:physiology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051785:Smad Proteins; D015534:Trans-Activators / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D009396:Wilms Tumor / Q000235:genetics* / Q000473:pathology
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D051785:Smad Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D014212:Tretinoin