Disease relevance of Wt1

• Oxygen-regulated expression of the Wilms' tumor suppressor Wt1 involves hypoxia-inducible factor-1 (HIF-1) [1].
• The promoter of the Wt1 gene was capable of mediating expression of a luciferase reporter in response to hypoxia [1].
• Wt1 expression was enhanced in the osteosarcoma line U-2OS and in Reh lymphoblast cells that were grown either at 1% O2 or in the presence of CoCl2 and desferrioxamine, respectively [1].
• Herein, we did transcriptional profiling using oligonucleotide microarrays of WISH-WT, WT source, human fetal and adult kidneys, and primary and metastatic renal cell carcinoma [2].
• Wilms tumor is a pediatric kidney cancer that has been linked to the inactivation of a tumor-suppressor gene at chromosome locus 11p13 [3].

High impact information on Wt1

• A dominant mutation in the Wilms tumor gene WT1 cooperates with the viral oncogene E1A in transformation of primary kidney cells [3].
• Wilms' tumor (WT), the embryonic kidney malignancy, is suggested to evolve from a progenitor cell population of uninduced metanephric blastema, which typically gives rise to nephrons [2].
• Thus, multiple imprinted and stemness genes that function to expand the renal progenitor cell population may lead to evolution and maintenance of WT [2].
• However, apart from blastema, WT specimens frequently contain cells that have differentiated into renal tubular or stromal phenotypes, complicating their analysis [2].
• The Wilms' tumor 1 gene (WT1) encodes a transcription factor of the zinc-finger family and is homozygously mutated or deleted in a subset of Wilms' tumors [4].

Chemical compound and disease context of Wt1

• We show here that Wt1 mRNA and protein is up-regulated in the heart and kidneys of rats exposed to normobaric hypoxia (8% O2) [1].
• PPARgamma expression in CONT at 12 weeks was increased in podocytes and in mesangial WT-1 cells in segmentally sclerotic glomeruli, with less Wilms' tumor 1 (WT-1) staining [5].

Biological context of Wt1

• Assignment of the Wilms' tumor (Wt1) gene to rat chromosome bands 3q34-->q35 by in situ hybridization [6].
• Our results indicate that impairment of DNA binding of the WT1 tumor-suppressor gene product can result in a dominant negative mutation [3].
• WT1, a gene deleted in some Wilms' tumors, encodes a transcription factor with zinc fingers and shares homology with proteins in the early growth response gene family [7].
• Cotransfection of a WT1 expression vector with a promoter reporter plasmid of inhibin-alpha resulted in the repression of promoter activities in CHO cells in a dose-dependent manner [7].
• In addition, the actions of p53 may be amplified through a cooperative interaction with another tumor suppressor protein, the product of the Wilms' tumor suppressor gene (WT-1) [8].

Anatomical context of Wt1

• We recently described de novo expression of Wt1 in myocardial blood vessels of ischemic rat hearts [1].
• In P6 rats, mesangial WT-1 staining was lessened, but podocyte staining was strongly accentuated [5].
• These results suggest that WT1 is expressed in high levels in granulosa cells of primordial, primary, and secondary follicles but decreases with follicle development [7].
• We have previously shown that expression of the WT1(-/-) isoform, lacking both inserts, increases the tumor growth rate of the adenovirus-transformed baby rat kidney (AdBRK) cell line 7C3H2, whereas expression of the WT1(-/+) isoform, lacking the 17aa insert, strongly suppresses the tumorigenic phenotype [4].
• Abundant WT1 transcripts were found in the ovary, testis, uterus, and kidney, with lower levels in the heart and pancreas [7].

Associations of Wt1 with chemical compounds

• Treatment with estrogen or gonadotropins did not affect the concentration of ovarian WT1 mRNA [7].
• Cyclin D3, important in cell cycle progression and Wilms tumor 1, related to cancer development, were also up-regulated in the vitamin E deficient animals [9].

Other interactions of Wt1

• Ectopic Wt1 immunoreactivity was detected in renal tubules of hypoxic rats, which also expressed the antiapoptotic protein Bcl-2 and contained significantly fewer TUNEL-positive cells than in normoxic kidneys [1].

Analytical, diagnostic and therapeutic context of Wt1

• We aimed to define tumor-progenitor genes that function in normal kidney development using WT xenografts (WISH-WT), in which the blastema accumulates with serial passages at the expense of differentiated cells [2].
• We investigated the expression of WT1 transcripts in rat ovary during follicle development by Northern blotting, RNase protection assay, and in situ hybridization [7].
• Subcutaneous injection of immature rats with 10 IU equine CG (eCG) reduced the levels of p53 and WT-1 mRNA to 71 +/- 9% (P < 0.05) and 46 +/- 3% (P < 0.05), respectively, of saline-treated control levels after 2 days [8].
• Unilateral nephrectomy induces the expression of the Wilms tumor gene in the contralateral kidney of the adult rat [10].
• Receptors on tumor cells bind factors which, when eluted followed by in vivo bioassay, stimulate the growth of Wilms tumor [11].

References