Wilms' tumor 1 gene (WT1) is overexpressed and provides an oncogenic function in pediatric nephroblastomas harboring the wild-type WT1

Sangkhathat,Surasak; Kanngurn,Samornmas; Chaiyapan,Welawee; Gridist,Podchanaporn; Maneechay,Wanwisa

doi:10.3892/ol_00000109

July-August 2010 Volume 1 Issue 4

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July-August 2010 Volume 1 Issue 4

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Article

Wilms' tumor 1 gene (WT1) is overexpressed and provides an oncogenic function in pediatric nephroblastomas harboring the wild-type WT1

Authors:
- Surasak Sangkhathat
- Samornmas Kanngurn
- Welawee Chaiyapan
- Podchanaporn Gridist
- Wanwisa Maneechay
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Affiliations: Tumor Biology Research Unit, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand. surasak.sa@psu.ac.th
Pages: 615-619
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Published online on: July 1, 2010

https://doi.org/10.3892/ol_00000109
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Abstract

Wilms' tumor 1 gene (WT1) is known to be a tumor suppressor gene in the subset of nephroblastomas that harbors WT1 mutations. However, its role in nephroblastomas without mutations remains unclear. This study aimed to evaluate the expression of WT1 and its potential oncogenic role in pediatric nephroblastoma with wild-type WT1. A total of 24 nephroblastomas were studied for WT1 mRNA expression by quantitative reverse-transcription polymerase chain reaction. The expression levels were compared between nephro-blastomas with and without WT1 mutations, as well as to normal kidney tissue, other pediatric renal tumors and neuroblastomas. Immunohistochemistry was used to evaluate expression patterns at the tissue level. Post-transcriptional inhibition of WT1 was performed in primary cultures of wild-type nephroblastoma using WT1 siRNA. The average WT1 expression level in nephroblastoma tissue was significantly higher than that in normal kidney tissue and neuroblastomas. Expression at the mRNA level was not different between nephroblastomas with WT1 mutations (4 cases) and those with wild-type WT1 (20 cases). However, while WT1 immunoreactivity was positive in all of the nephroblastoma components in the tumors with wild-type WT1, the protein expression was weaker and limited to stromal components in the tumors with mutated WT1, where it co-localized with β-catenin nuclear accumulation. The post-transcriptional inhibition of WT1 resulted in growth retardation and a significantly increased apoptotic fraction. Our study found overexpression of the WT1 gene in pediatric nephroblastomas with wild-type WT1. Moreover, the study suggests an oncogenic role of WT1 in this tumor subset.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Wilms' tumor 1 gene (WT1) is overexpressed and provides an oncogenic function in pediatric nephroblastomas harboring the wild-type WT1

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