Online citations, reference lists, and bibliographies.
← Back to Search

Target Genes Of The WNT/β‐catenin Pathway In Wilms Tumors

B. Zirn, B. Samans, S. Wittmann, T. Pietsch, I. Leuschner, N. Graf, M. Gessler
Published 2006 · Biology

Cite This
Download PDF
Analyze on Scholarcy
Share
The WNT/β‐catenin pathway is involved in numerous human cancers. Mutations of the CTNNB1 (β‐catenin) gene have also been detected in a subset of pediatric Wilms tumors, but the target genes of the deregulated WNT/β‐catenin pathway in these tumors have yet to be identified. To compare gene expression profiles of Wilms tumors with and without mutations of CTNNB1, we used 11.5‐k cDNA microarrays. Most of the tumors (86%) had received preoperative chemotherapy as mandated by the European SIOP protocol. The comparison between Wilms tumors with and without CTNNB1 mutations revealed several target genes specifically deregulated in CTNNB1‐mutated Wilms tumors. Among these, PITX2, APCDD1, and two members of the endothelin axis (EDN3 and EDNRA) are directly activated downstream targets of the WNT/β‐catenin pathway that may enhance proliferation of these tumor cells. In addition, several upstream inhibitors of WNT/β‐catenin signaling like WIF1 and PRDC were also strongly up‐regulated in the CTNNB1‐mutated Wilms tumors. This overexpression may be a negative feedback mechanism in tumors with uncontrolled WNT signaling. Moreover, we identified deregulated genes in both the retinoic acid and the RAS pathways, such as ATX/ENPP2 and RIS1, suggesting an association between these two pathways with that of WNT. In addition, the strong representation of muscle‐related genes in the expression profile of CTNNB1‐mutated Wilms tumors corresponded to histologically detectable areas of myomatous cells in these tumors that displayed intense and preferential nuclear β‐catenin antibody staining. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat. © 2006 Wiley‐Liss, Inc.
This paper references
Regulation of vascular endothelial growth factor by the Wnt and K-ras pathways in colonic neoplasia.
X. Zhang (2001)
10.1126/SCIENCE.275.5307.1790
Stabilization of β-Catenin by Genetic Defects in Melanoma Cell Lines
B. Rubinfeld (1997)
10.1016/S0006-291X(02)00828-8
Drm/Gremlin transcriptionally activates p21(Cip1) via a novel mechanism and inhibits neoplastic transformation.
B. Chen (2002)
10.1016/S0959-8049(99)00128-8
Fetal rhabdomyomatous nephroblastoma: a tumour of good prognosis but resistant to chemotherapy.
P. Maes (1999)
10.3892/IJMM.10.4.395
Codon 45 of the β-catenin gene, a specific mutational target site of Wilms' tumor
T. Kusafuka (2002)
10.1074/JBC.M200334200
Synergistic Induction of Tumor Antigens by Wnt-1 Signaling and Retinoic Acid Revealed by Gene Expression Profiling*
D. Tice (2002)
10.1200/JCO.2003.04.176
Effect of endothelin-A receptor blockade with atrasentan on tumor progression in men with hormone-refractory prostate cancer: a randomized, phase II, placebo-controlled trial.
M. Carducci (2003)
10.1126/SCIENCE.281.5382.1509
Identification of c-MYC as a target of the APC pathway.
T. He (1998)
10.1038/45803
Pitx2 regulates lung asymmetry, cardiac positioning and pituitary and tooth morphogenesis
C. Lin (1999)
Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells.
O. Tetsu (1999)
10.1186/gb-2003-4-10-r70
Identifying biological themes within lists of genes with EASE
Douglas A. Hosack (2003)
10.1016/S0960-9822(00)80088-3
Cross-regulation of β-catenin–LEF/TCF and retinoid signaling pathways
V. Easwaran (1999)
10.1006/EXCR.2001.5434
Identification of a candidate tumor-suppressor gene specifically activated during Ras-induced senescence.
M. Barradas (2002)
10.1097/01.LAB.0000059926.66359.BD
Overexpression of Human Dickkopf-1, an Antagonist of wingless/WNT Signaling, in Human Hepatoblastomas and Wilms’ Tumors
O. Wirths (2003)
Frequent Association of β-Catenin and WT1 Mutations in Wilms Tumors
S. Maiti (2000)
10.1016/J.CANLET.2004.08.001
Chibby, a novel antagonist of the Wnt pathway, is not involved in Wilms tumor development.
B. Zirn (2005)
10.1038/sj.onc.1208725
All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo
B. Zirn (2005)
Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC
PJ Morin (1997)
Codon 45 of the beta-catenin gene, a specific mutational target site of Wilms' tumor.
T. Kusafuka (2002)
Cross-regulation of beta-catenin-LEF/TCF and retinoid signaling pathways.
V. Easwaran (1999)
Stabilization of beta-catenin by genetic defects in melanoma cell lines.
B. Rubinfeld (1997)
10.1002/(SICI)1096-8628(19981002)79:4<260::AID-AJMG6>3.0.CO;2-Q
Wilms tumor genetics.
V. Huff (1998)
Isolation of a novel human gene, APCDD1, as a direct target of the beta-Catenin/T-cell factor 4 complex with probable involvement in colorectal carcinogenesis.
M. Takahashi (2002)
Effect of endothe - linA receptor blockade with atrasentan on tumor progression in men with hormone - refractory prostate cancer : a randomized , phase II , placebo - controlled trial
MA Carducci (2003)
10.1002/ijc.21564
Expression profiling of Wilms tumors reveals new candidate genes for different clinical parameters
B. Zirn (2006)
10.1002/HUMU.1380030307
Infrequent mutation of the WT1 gene in 77 Wilms' tumors
M. Gessler (1994)
10.1016/0092-8674(93)90515-R
WT-1 is required for early kidney development
J. Kreidberg (1993)
Childhood hepatoblastomas frequently carry a mutated degradation targeting box of the beta-catenin gene.
A. Koch (1999)
Frequent association of beta-catenin and WT1 mutations in Wilms tumors.
S. Maiti (2000)
Mutational activation of the beta-catenin proto-oncogene is a common event in the development of Wilms' tumors.
R. Koesters (1999)
10.1016/S0002-9440(10)63246-4
CTNNB1 mutations and overexpression of Wnt/beta-catenin target genes in WT1-mutant Wilms' tumors.
C. Li (2004)
Two molecular subgroups of Wilms' tumors with or without WT1 mutations.
V. Schumacher (2003)
10.1016/S0092-8674(02)01084-X
Identification of a Wnt/Dvl/β-Catenin → Pitx2 Pathway Mediating Cell-Type-Specific Proliferation during Development
C. Kioussi (2002)
10.1002/path.1449
WIF1, a component of the Wnt pathway, is down‐regulated in prostate, breast, lung, and bladder cancer
C. Wissmann (2003)
10.1074/jbc.M404587200
Interaction, Cooperative Promoter Modulation, and Renal Colocalization of GCMa and Pitx2*
S. W. Schubert (2004)
10.1242/jcs.00623
Secreted antagonists of the Wnt signalling pathway
Y. Kawano (2003)
10.1002/BIES.20081
The ins and outs of lysophosphatidic acid signaling
W. Moolenaar (2004)
10.1038/NG0198-15
Loss of WT1 function leads to ectopic myogenesis in Wilms' tumour
K. Miyagawa (1998)



This paper is referenced by
10.1227/NEU.0b013e3181ec7b71
Global Gene Expression Profiling and Tissue Microarray Reveal Novel Candidate Genes and Down-Regulation of the Tumor Suppressor Gene CAV1 in Sporadic Vestibular Schwannomas
M. Aarhus (2010)
10.1016/j.mce.2010.02.039
Identification of Wnt family inhibitors: A pituitary tumor directed whole genome approach
M. Elston (2010)
10.1210/jc.2010-2143
Characterization of differential gene expression in adrenocortical tumors harboring beta-catenin (CTNNB1) mutations.
Julien Durand (2011)
Generation and analysis of mouse models of aberrant β-catenin function
P. R. Cuadrado (2011)
10.1002/ijc.28768
Multilayer-omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome
E. Arai (2014)
10.1002/gcc.20387
Neuroblastoma tumors with favorable and unfavorable outcomes: Significant differences in mRNA expression of genes mapped at 1p36.2
S. Fransson (2007)
10.1002/path.2524
Gene expression profiling provides insights into the pathways involved in solid pseudopapillary neoplasm of the pancreas
C. Cavard (2009)
10.1016/j.ydbio.2014.12.031
Wnt7b is required for epithelial progenitor growth and operates during epithelial-to-mesenchymal signaling in pancreatic development.
Solomon Afelik (2015)
10.1074/jbc.M115.678029
Wilms Tumor Suppressor, WT1, Cooperates with MicroRNA-26a and MicroRNA-101 to Suppress Translation of the Polycomb Protein, EZH2, in Mesenchymal Stem Cells*
Murielle M. Akpa (2015)
Caractérisation de l'implication de β-caténine dans les tumeurs surrénaliennes.
Julien Durand (2011)
10.1016/j.celrep.2012.09.015
A small molecule that promotes cardiac differentiation of human pluripotent stem cells under defined, cytokine- and xeno-free conditions.
Itsunari Minami (2012)
10.1002/art.27282
Comparative analysis of gene expression profiles between primary knee osteoarthritis and an osteoarthritis endemic to Northwestern China, Kashin-Beck disease.
C. Duan (2010)
10.1016/j.bbrc.2017.07.049
Epigenetic silencing of the Wnt antagonist APCDD1 by promoter DNA hyper-methylation contributes to osteosarcoma cell invasion and metastasis.
Weifeng Han (2017)
10.1080/01635581.2019.1650192
Silencing of TMEM158 Inhibits Tumorigenesis and Multidrug Resistance in Colorectal Cancer
Lihua Liu (2019)
10.3390/ijms151017852
Intersection of AHR and Wnt Signaling in Development, Health, and Disease
A. J. Schneider (2014)
10.1111/j.1600-0609.2011.01592.x
Physiological inhibitors of Wnt signaling
A. Filipovich (2011)
10.1371/journal.pone.0010456
A Novel Role for Wnt/Ca2+ Signaling in Actin Cytoskeleton Remodeling and Cell Motility in Prostate Cancer
Q. Wang (2010)
10.1007/s12032-016-0862-5
K-Ras, H-Ras, N-Ras and B-Raf mutation and expression analysis in Wilms tumors: association with tumor growth
E. Dalpa (2016)
10.1371/journal.pone.0037076
Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression
F. K. Fung (2012)
10.1002/gcc.20686
WNT/β‐catenin pathway activation in Wilms tumors: A unifying mechanism with multiple entries?
Marie Corbin (2009)
10.1007/978-3-662-44003-2_10
Molecular-Targeted Therapy for Pediatric Renal Tumors
J. Geller (2014)
10.1002/cncr.23672
Clinical relevance of mutations in the Wilms tumor suppressor 1 gene WT1 and the cadherin‐associated protein β1 gene CTNNB1 for patients with Wilms tumors
B. Royer-Pokora (2008)
10.1186/1471-2164-9-359
Transcriptional profiling of putative human epithelial stem cells
S. S. Koçer (2007)
10.1371/journal.pone.0122333
Transcriptome Analysis of Wnt3a-Treated Triple-Negative Breast Cancer Cells
Sylvie Maubant (2015)
10.1016/j.ajpath.2011.08.006
β-Catenin and K-RAS synergize to form primitive renal epithelial tumors with features of epithelial Wilms' tumors.
P. Clark (2011)
10.1016/j.bbrc.2014.12.107
The WNT inhibitor APCDD1 sustains the expression of β-catenin during the osteogenic differentiation of human dental follicle cells.
S. Viale-Bouroncle (2015)
10.1016/j.biocel.2009.12.006
Lymphoid enhancer factor-1 mediates loading of Pax3 to a promoter harbouring lymphoid enhancer factor-1 binding sites resulting in enhancement of transcription.
T. Christova (2010)
10.1007/s00383-016-3970-6
Activation of the Wnt/β-catenin pathway is common in wilms tumor, but rarely through β-catenin mutation and APC promoter methylation
Amei Schweigert (2016)
10.1210/en.2012-1564
Wnt inhibitory factor 1 (Wif1) is regulated by androgens and enhances androgen-dependent prostate development.
Kimberly P Keil (2012)
10.1002/mc.20361
Transcriptome analysis of serous ovarian cancers identifies differentially expressed chromosome 3 genes
A. Birch (2008)
10.1186/s13046-015-0193-y
Overexpression of TMEM158 contributes to ovarian carcinogenesis
Z. Cheng (2015)
Mechanisms and Consequences of Chromosomal Instability in Malignant tumours
Y. Stewénius (2008)
See more
Semantic Scholar Logo Some data provided by SemanticScholar