Human Gene Set: ZIRN_TRETINOIN_RESPONSE_WT1_DN


Standard name ZIRN_TRETINOIN_RESPONSE_WT1_DN
Systematic name M7641
Brief description Genes down-regulated in MZ128 cells (Wilms tumor with mutated WT1 [GeneID=7490]) after treatment with 10 microM tretinoin (ATRA) [PubChem=444795] for 24 h.
Full description or 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 (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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15897880   Authors: Zirn B,Samans B,Spangenberg C,Graf N,Eilers M,Gessler M
Exact source Table 1: Fold change in MZ128 < 0
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Source species Homo sapiens
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