Functional Role of WT1 in Prostate Cancer
| Autor: | Nirmala Ghimirey, Sarah Nock, Sony Pandey, Gail Fraizer, Anton Bazarov, Steven J. Kuerbitz, Adina Brett-Morris, Kurtis Eisermann |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Angiogenic Switch Biology urologic and male genital diseases 03 medical and health sciences Prostate cancer chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Internal medicine medicine Transcriptional regulation urogenital system fungi Wilms' tumor Cell migration medicine.disease female genital diseases and pregnancy complications Androgen receptor Vascular endothelial growth factor 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cancer research |
| Zdroj: | Wilms Tumor ISBN: 9780994438119 |
| DOI: | 10.15586/codon.wt.2016.ch14 |
| Popis: | Although initial discoveries of Wilms tumor 1 (WT1) expression in extrarenal disease generated controversy, we and others have examined WT1 expression in non-Wilms cancers and have demonstrated that the WT1(A) isoform, lacking the lysine-threonine-serine tripeptide (KTS) insertion, transcriptionally regulates the expression of growth control genes in other cancer types. Here, we review our evidence that WT1 is expressed in prostate cancer (PC) epithelial cells and regulates PC critical genes. That WT1 may promote metastatic disease is consistent with previous findings that WT1 suppressed E-cadherin and enhanced motility of PC cells with low migratory and metastatic potential. Recent findings led us to ask whether WT1 acts as an angiogenic switch in PC. Although vascular endothelial growth factor (VEGF) is regulated at several levels and by a number of different factors, a mechanistic understanding of WT1-mediated transcriptional regulation in PC cells was previously lacking. Here, we discuss the evidence of WT1- and androgen receptor (AR)-binding sites in the VEGF promoter and show the potential for cooperation between hormone and WT1. These findings revealed that in AR-intact PC cells, WT1 was sufficient to upregulate VEGF transcription, and WT1 expression enhanced the hormone activation of VEGF expression. This notion that WT1 can activate an angiogenic switch in PC cells, to enhance tumor growth and progression to metastatic disease, is consistent with our understanding of the oncogenic nature of WT1 overexpression in inappropriate tissues or at inappropriate times. The potential for WT1 to promote both tumor angiogenesis and PC cell migration suggests that WT1 regulates genes that promote PC progression to lethal metastatic disease. Therapies targeting WT1 in PC may reduce metastatic spread and increase overall survival. |
| Databáze: | OpenAIRE |
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