ArticleBritish journal of cancer2010
Wilms' tumour 1 can suppress hTERT gene expression and telomerase activity in clear cell renal cell carcinoma via multiple pathways.
Article in British journal of cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- Review
- Telomerase Regulation: A Role for Epigenetics.Cancers · 2021Review
- A Novel Liquid Biopsy Strategy to Detect Small Amounts of Cancer Cells Using Cancer-Specific Replication Adenoviruses.Journal of clinical medicine · 2020Review
- The Effects of Proteasome Inhibitors on Telomerase Activity and Regulation in Multiple Myeloma Cells.International journal of molecular sciences · 2019Article
- Wilms' tumor 1-associating protein promotes renal cell carcinoma proliferation by regulating CDK2 mRNA stability.Journal of experimental & clinical cancer research : CR · 2018Article
- Aberrant expression of ETS1 and ETS2 proteins in cancer.Cancer reports and reviews · 2018Article
- Functional dissection of breast cancer risk-associatedOncotarget · 2017Article
- Distinct global binding patterns of the Wilms tumor gene 1 (WT1) -KTS and +KTS isoforms in leukemic cells.Haematologica · 2017Article
- Human telomerase reverse transcriptase regulation by DNA methylation, transcription factor binding and alternative splicing (Review).International journal of oncology · 2016Review
- Review
- Telomerase: The Devil Inside.Genes · 2016Review
- Wilms' tumor gene 1 regulates p63 and promotes cell proliferation in squamous cell carcinoma of the head and neck.BMC cancer · 2015Article
- Prognostic significance of specific anti-WT1 IgG antibody level in plasma in patients with ovarian carcinoma.Cancer medicine · 2014Article
- Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms.PLoS computational biology · 2014Article
- How far is the horizon? From current targets to future drugs in advanced renal cancer.World journal of urology · 2014Review
- Single nucleotide polymorphisms in the Wilms' tumour gene 1 in clear cell renal cell carcinoma.PloS one · 2013Article
- Tumor suppressors p53, p63TAα, p63TAy, p73α, and p73β use distinct pathways to repress telomerase expression.The Journal of biological chemistry · 2012Article
- Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWilms' tumour 1 (WT1) gene was discovered as a tumour suppressor gene. Later findings have suggested that WT1 also can be oncogenic. This complexity is partly explained by the fact that WT1 has a number of target genes.
methodWT1 and its target gene human telomerase reverse transcriptase (hTERT) were analysed in clear cell renal cell carcinoma (ccRCC). In vitro experiments were performed to examine the functional link between WT1 and hTERT by overexpression of WT1 isoforms in the ccRCC cell line, TK-10.
resultsWT1 demonstrated lower RNA expression in ccRCC compared with renal cortical tissue, whereas hTERT was increased, showing a negative correlation between WT1 and hTERT (P=0.005). These findings were experimentally confirmed in vitro. The WT1 generated effect on hTERT promoter activity seemed complex, as several negative regulators of hTERT transcription, such as SMAD3, JUN (AP-1) and ETS1, were activated by WT1 overexpression. Downregulation of potential positive hTERT regulators, such as cMyc, AP-2α, AP-2γ, IRF1, NFX1 and GM-CSF, were also observed. Chromatin immunoprecipitation analysis verified WT1 binding to the hTERT, cMyc and SMAD3 promoters.
conclusionThe collected data strongly indicate multiple pathways for hTERT regulation by WT1 in ccRCC.
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