Sökning: WFRF:(Sitaram Raviprakash T)
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Wilms' tumour 1 can...
Wilms' tumour 1 can suppress hTERT gene expression and telomerase activity in clear cell renal cell carcinoma via multiple pathways
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- Sitaram, Raviprakash T, 1974- (författare)
- Umeå universitet,Patologi
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- Degerman, Sofie (författare)
- Umeå universitet,Patologi
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- Ljungberg, Börje (författare)
- Umeå universitet,Urologi och andrologi
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- Andersson, Emma (författare)
- Umeå universitet,Patologi
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- Oji, Y (författare)
- Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan
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- Sugiyama, H (författare)
- Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan
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- Roos, Göran (författare)
- Umeå universitet,Patologi
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- Li, Ai-Hong (författare)
- Umeå universitet,Klinisk kemi
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(creator_code:org_t)
- 2010-09-14
- 2010
- Engelska.
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 103:8, s. 1255-1262
- Relaterad länk:
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- BACKGROUND: Wilms' 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. METHOD: WT1 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. RESULTS: WT1 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. CONCLUSION: The collected data strongly indicate multiple pathways for hTERT regulation by WT1 in ccRCC.
Nyckelord
- renal cell carcinoma; WT1; hTERT; telomerase activity and pathways
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- ref (ämneskategori)
- art (ämneskategori)
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