Wilms tumor 1 expression in malignant gliomas and correlation of +KTS isoforms with p53 status

Clark, Aaron J.; Santos, Wagner Gouvêa dos; McCready, Jessica; Chen, Mike Y; Meter, Timothy E. Van; Ware, Joy L.; Wolber, Sharon B; Fillmore, Helen; Broaddus, William C.

doi:10.3171/jns-07/09/0586

Cited by 30 publications

(36 citation statements)

References 36 publications

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“…3 It was reported in follow-up work that there was an interaction between the KTS + isoform of WT1 and wild-type p53, revealing that the potential oncogenic function of WT1 in GBM may depend on this splicing variant. 7 Additional avenues whereby WT1 promotes tumorigenesis was found in WT1's relation with Wilms tumor 1-associated protein (WTAP, also known as pre-mRNAsplicing regulator WTAP). WTAP is a nuclear protein that was isolated through a yeast 2-hybrid screen and has been reported to be overexpressed in GBM cell lines.…”

Section: Gbm and Wilms Tumormentioning

confidence: 99%

“…Recently, our laboratory and others have shifted their focus to the Wilms tumor 1 gene (WT1). [5][6][7][8] WT1 was first isolated in 1990 by Haber et al with their discovery that an internal deletion within an 11p13 zinc finger gene contributes to the development of Wilms tumor, a pediatric kidney malignancy. 10 WT1 was initially thought to be a tumor suppressor gene, but subsequent research uncovered its oncogenic role when it was demonstrated that WT1 can suppress hTERT gene expression and telomerase activity in clear cell renal cell carcinoma.…”

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Wilms tumor 1 gene, CD97, and the emerging biogenetic profile of glioblastoma

Somasundaram

Ardanowski

Opalak

et al. 2014

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Glioblastoma multiforme (GBM) is the most common type of primary brain tumor, and current treatment regimens are only marginally effective. One of the most vexing and malignant aspects of GBM is its pervasive infiltration into surrounding brain tissue. This review describes the role of the Wilms tumor 1 gene (WT1) and its relationship to GBM. WT1 has several alternative splicing products, one of which, the KTS+ variant, has been demonstrated to be involved in the transcriptional activation of a variety of oncogenes as well as the inhibition of tumor suppressor genes. Further, this paper will examine the relationship of WT1 with CD97, a gene that codes for an epidermal growth factor receptor family member, an adhesion G-protein–coupled receptor, thought to promote tumor invasiveness and migration. The authors suggest that further research into WT1 and CD97 will allow clinicians to begin to deal more effectively with the infiltrative behavior displayed by GBM and design new therapies that target this deadly disease.

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Section: Gbm and Wilms Tumormentioning

confidence: 99%

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confidence: 99%

Wilms tumor 1 gene, CD97, and the emerging biogenetic profile of glioblastoma

Somasundaram

Ardanowski

Opalak

et al. 2014

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“…3,6,7,10,11,18,22,[24][25][26][27][28][29][30][31]34,36,38,39,42 We have previously demonstrated WT1 expression in approximately 80% of glioma cell lines and tumor speciNovel report of expression and function of CD97 in malignant gliomas: correlation with Wilms tumor 1 expression and glioma cell invasiveness mens. 5 The predominant WT1 isoform expressed in these cells contained a 17-amino acid peptide coded for by exon 5 and the tripeptide KTS between zinc fingers 3 and 4 (WT1 +/+). Our studies showed that glioma cells that had endogenous WT1 expression relied heavily on this protein for their growth and motility.…”

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confidence: 99%

Novel report of expression and function of CD97 in malignant gliomas: correlation with Wilms tumor 1 expression and glioma cell invasiveness

Chidambaram

Fillmore

Meter

et al. 2012

JNS

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Object. The Wilms tumor 1 (WT1) protein-a developmentally regulated transcription factor-is aberrantly expressed in gliomas and promotes their malignant phenotype. However, little is known about the molecular allies that help it mediate its oncogenic functions in glioma cells.Methods. The authors used short interfering RNA (siRNA) to suppress WT1 expression in glioblastoma (GBM) cells and evaluated the effect of this on GBM cell invasiveness. Gene expression analysis was then used to identify the candidate genes that were altered as a result of WT1 silencing. One candidate target, CD97, was then selected for further investigation into its role by suppressing its expression using siRNA silencing, followed by proliferation and invasion assays.Results. WT1 levels were reliably and reproducibly suppressed by siRNA application. This resulted in a significant decrease in cellular invasiveness. Microarray analyses identified the gene products that were consistently downregulated (27) and upregulated (11) with WT1 silencing. Of these, CD97 expression was consistently suppressed across the 3 different GBM cell lines studied and was found on further investigation to significantly impact GBM cell invasiveness.Conclusions. Although CD97 expression in gliomas has not been described previously, we conclude that the possible upregulation of CD97 mediated by WT1 promotes cellular invasiveness-one of the most characteristic and challenging aspects of glial tumor cells. Further studies are needed to clarify the nature of this regulation and its impact, as CD97 could represent a novel target for antiglioma therapies. (http://thejns.org/doi/abs/10.3171/2011.11.JNS111455) Key Words • Wilms tumor 1 • glioblastoma • invasiveness • target genes • oncology 843Abbreviations used in this paper: ATP = adenosine triphosphate; EGF = epidermal growth factor; GBM = glioblastoma; PDGF = platelet-derived growth factor; qRT-PCR = quantitative reverse transcriptase polymerase chain reaction; SDS = sodium dodecyl sulfate; siRNA = short interfering RNA; VCU = Virginia Commonwealth University; WT1 = Wilms tumor 1.

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“…In our experience expression is similar in primary and secondary tumors but expression can be reduced in recurrent tumors. In addition there is evidence that tumors that contain a Tp53 mutation show reduced WT1 levels compared to Tp53 wild type glioblastomas (Clark et al, 2007). IDH1 R132H antibody expression is found in 4% of primary and in 71% of secondary glioblastoma .…”

Section: Immunohistochemistrymentioning

confidence: 98%