scholarly journals Wilms' Tumor Suppressor GeneWT1

2000 ◽  
Vol 11 (suppl 2) ◽  
pp. S106-S115 ◽  
Author(s):  
CHRISTIAN MROWKA ◽  
ANDREAS SCHEDL
Keyword(s):  
Tumor Suppressor ◽  
Rna Editing ◽  
Kidney Development ◽  
Wilms Tumor ◽  
Suppressor Gene ◽  
Structural Features ◽  
Genomic Locus ◽  
Developmental Abnormalities ◽  
Complex Process

Abstract.Normal development of the kidney is a highly complex process that requires precise orchestration of proliferation, differentiation, and apoptosis. In the past few years, a number of genes that regulate these processes, and hence play pivotal roles in kidney development, have been identified. The Wilms' tumor suppressor geneWT1has been shown to be one of these essential regulators of kidney development, and mutations in this gene result in the formation of tumors and developmental abnormalities such as the Denys-Drash and Frasier syndromes. A fascinating aspect of theWT1gene is the multitude of isoforms produced from its genomic locus. In this review, our current understanding of the structural features ofWT1, how they modulate the transcriptional and post-transcriptional activities of the protein, and how mutations affecting individual isoforms can lead to diseased kidneys is summarized. In addition, results from transgenic experiments, which have yielded important findings regarding the function of WT1in vivo, are discussed. Finally, data on the unusual feature of RNA editing ofWT1transcripts are presented, and the relevance of RNA editing for the normal functioning of the WT1 protein in the kidney is discussed.

scholarly journals Analysis of the Wilms' Tumor Suppressor Gene (WT1) in Patients 46,XY Disorders of Sex Development

2011 ◽  
Vol 96 (7) ◽  
pp. E1131-E1136 ◽  
Author(s):  
B. Köhler ◽  
H. Biebermann ◽  
V. Friedsam ◽  
J. Gellermann ◽  
R. F. Maier ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Gonadal Dysgenesis ◽  
Kidney Development ◽  
Wilms Tumor ◽  
Disorders Of Sex Development ◽  
Suppressor Gene ◽  
Sex Development ◽  
Cryptorchid Testis

Abstract Context: The Wilms' tumor suppressor gene (WT1) is one of the major regulators of early gonadal and kidney development. WT1 mutations have been identified in 46,XY disorders of sex development (DSD) with associated kidney disease and in few isolated forms of 46,XY DSD. Objective: The objective of the study was the evaluation of WT1 mutations in different phenotypes of isolated 46,XY DSD and clinical consequences. Design: The design of the study was: 1) sequencing of the WT1 gene in 210 patients with 46,XY DSD from the German DSD network, consisting of 150 males with severe hypospadias (70 without cryptorchidism, 80 with at least one cryptorchid testis), 10 males with vanishing testes syndrome, and 50 raised females with partial to complete 46,XY gonadal dysgenesis; and 2) genotype-phenotype correlation of our and all published patients with 46,XY DSD and WT1 mutations. Results: We have detected WT1 mutations in six of 80 patients with severe hypospadias (7.5%) and at least one cryptorchid testis and in one of 10 patients with vanishing testes syndrome (10%). All patients except one developed Wilms' tumor and/or nephropathy in childhood or adolescence. Conclusion: WT1 analysis should be performed in newborns with complex hypospadias with at least one cryptorchid testis and in isolated 46,XY partial to complete gonadal dysgenesis. Kidney disease might not develop until later life in these cases. WT1 analysis is mandatory in all 46,XY DSD with associated kidney disease. WT1 analysis is not indicated in newborns with isolated hypospadias without cryptorchidism. Patients with WT1 mutations should be followed up closely because the risk of developing a Wilms' tumor, nephropathy, and/or gonadal tumor is very high.

Suppression of prostate tumor cell growth in vivo by WT1, the Wilms' tumor suppressor gene

2004 ◽  
Author(s):  
Gail Fraizer ◽  
Rachel Leahy ◽  
Subhadra Priyadarshini ◽  
Kylie Graham ◽  
Jorge Delacerda ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Suppressor ◽  
Tumor Cell ◽  
Tumor Suppressor Gene ◽  
Wilms Tumor ◽  
Suppressor Gene ◽  
Prostate Tumor ◽  
Tumor Cell Growth ◽  
Prostate Tumor Cell

scholarly journals Identification of Novel Wilms' Tumor Suppressor Gene Target Genes Implicated in Kidney Development

2007 ◽  
Vol 282 (22) ◽  
pp. 16278-16287 ◽  
Author(s):  
Ho-Shik Kim ◽  
Myoung Shin Kim ◽  
Anne L. Hancock ◽  
James C. P. Harper ◽  
Jik Young Park ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Target Genes ◽  
Kidney Development ◽  
Wilms Tumor ◽  
Suppressor Gene ◽  
Gene Target

Wt1-expressing progenitors contribute to multiple tissues in the developing lung

2013 ◽  
Vol 305 (4) ◽  
pp. L322-L332 ◽  
Author(s):  
Elena Cano ◽  
Rita Carmona ◽  
Ramón Muñoz-Chápuli
Keyword(s):  
Smooth Muscle ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Fluorescent Protein ◽  
Wilms Tumor ◽  
Yellow Fluorescent Protein ◽  
Suppressor Gene ◽  
Differentiation Potential ◽  
Mesenchymal Transition ◽  
Lung Morphogenesis

Lungs develop from paired endodermal outgrowths surrounded by a mesodermal mesenchyme. Part of this mesenchyme arises from epithelial-mesenchymal transition of the mesothelium that lines the pulmonary buds. Previous studies have shown that this mesothelium-derived mesenchyme contributes to the smooth muscle of the pulmonary vessels, but its significance for lung morphogenesis and its developmental fate are still little known. We have studied this issue using the transgenic mouse model mWt1/IRES/GFP-Cre (Wt1cre) crossed with the Rosa26R-EYFP reporter mouse. In the developing lungs, Wt1, the Wilms' tumor suppressor gene, is specifically expressed in the embryonic mesothelium. In the embryos obtained from the crossbreeding, the Wt1-expressing cell lineage produces the yellow fluorescent protein (YFP), allowing for colocalization with differentiation markers. Wt1cre-YFP cells were very abundant from the origin of the lung buds to postnatal stages, contributing significantly to pulmonary endothelial and smooth muscle cells, bronchial musculature, tracheal and bronchial cartilage, as well as CD34+ fibroblast-like interstitial cells. Thus Wt1cre-YFP mesenchymal cells show the very same differentiation potential as the splanchnopleural mesenchyme surrounding the lung buds. FSP1+ fibroblast-like cells were always YFP−; they expressed the common leukocyte antigen CD45 and were apparently recruited from circulating progenitors. We have also found defects in pulmonary development in Wt1−/− embryos, which showed abnormally fused lung lobes, round-shaped and reduced pleural cavities, and diaphragmatic hernia. Our results suggest a novel role for the embryonic mesothelium-derived cells in lung morphogenesis and involve the Wilms' tumor suppressor gene in the development of this organ.

scholarly journals Possible Correlation between Hypomelanosis of Ito and Wilms’ Tumor

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Daniella Bello-Germino ◽  
Rasmey Chhin ◽  
Thu Tran ◽  
Tetyana L. Vasylyeva
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tumor Suppressor ◽  
Wilms Tumor ◽  
Tumor Stage ◽  
Suppressor Gene ◽  
Hypomelanosis Of Ito ◽  
Neurocutaneous Disorder ◽  
Clinical Diagnoses ◽  
Organ Dysfunctions

Hypomelanosis of Ito is a neurocutaneous disorder characterized by skin manifestations in a characteristic pattern associated with musculoskeletal and central nervous system symptoms. Our patient was diagnosed with Wilms’ tumor stage I at age two and was also found to have distinct streaked areas of skin hyper- and hypopigmentation suggestive of Hypomelanosis of Ito. We believe that our patient’s clinical diagnoses of Hypomelanosis of Ito and Wilms’ tumor are interlinked. The connecting factor is yet to be identified. Our patient does not have a deletion of 11p13 associated with a defect in WT1, the Wilms’ tumor suppressor gene. As such, it is quite possible that what made her more susceptible to the development of Wilms’ tumor was her Hypomelanosis of Ito, which is implicated in a number of other organ dysfunctions.

scholarly journals Wilms' Tumor Gene (WT1) Competes With Differentiation-Inducing Signal in Hematopoietic Progenitor Cells

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2969-2976 ◽  
Author(s):  
Kazushi Inoue ◽  
Hiroya Tamaki ◽  
Hiroyasu Ogawa ◽  
Yoshihiro Oka ◽  
Toshihiro Soma ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Tumor Suppressor ◽  
Progenitor Cells ◽  
Wilms Tumor ◽  
Suppressor Gene ◽  
Hematopoietic Progenitor Cells ◽  
Wt1 Gene ◽  
Wild Type ◽  
Hematopoietic Progenitor ◽  
Oncogenic Function

The WT1 gene is a tumor-suppressor gene that was isolated as a gene responsible for Wilms' tumor, a childhood kidney neoplasm. We have previously reported that the WT1 gene is strongly expressed in leukemia cells with an increase in its expression levels at relapse and an inverse correlation between its expression levels and prognosis, thus making it a novel tumor marker for leukemic blast cells. Furthermore, WT1 antisense oligomers have been found to inhibit the growth of leukemic cells. These results strongly suggested the involvement of the WT1 gene in human leukemogenesis. The present study was performed to prove our hypothesis that the WT1 gene plays a key role in leukemogenesis and performs an oncogenic function in hematopoietic progenitor cells, rather than a tumor-suppressor gene function. 32D cl3, an interleukin-3–dependent myeloid progenitor cell line, differentiates into mature neutrophils in response to granulocyte colony-stimulating factor (G-CSF). However, when transfected wild-type WT1 gene was constitutively expressed in 32D cl3, the cells stopped differentiating and continued to proliferate in response to G-CSF. As for signal transduction mediated by G-CSF receptor (G-CSFR), Stat3α was constitutively activated in wild-type WT1-infected 32D cl3 in response to G-CSF, whereas, in WT1-uninfected 32D cl3, activation of Stat3α was only transient. However, most interesting was the fact that G-CSF stimulation resulted in constitutive activation of Stat3β only in wild-type WT1-infected 32D cl3, but not in WT1-uninfected 32D cl3. Thus, WT1 expression constitutively activated both Stat3α and Stat3β. A transient activation of Stat1 was detected in both wild-type WT1-infected and uninfected 32D cl3 after G-CSF stimulation, but no difference in its activation was found. No activation of MAP kinase was detected in both wild-type WT1-infected and uninfected 32D cl3 after G-CSF stimulation. These results demonstrated that WT1 expression competed with the differentiation-inducing signal mediated by G-CSFR and constitutively activated Stat3, resulting in the blocking of differentiation and subsequent proliferation. Therefore, the data presented here support our hypothesis that the WT1 gene plays an essential role in leukemogenesis and performs an oncogenic function in hematopoietic progenitor cells and represent the first demonstration of an important role of the WT1 gene in signal transduction in hematopoietic progenitor cells.

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