TITLE

Wilms' tumour 1 can suppress hTERT gene expression and telomerase activity in clear cell renal cell carcinoma via multiple pathways

AUTHOR(S)
Sitaram, R. T.; Degerman, S.; Ljungberg, B.; Andersson, E.; Oji, Y.; Sugiyama, H.; Roos, G.; Li, A.
PUB. DATE
October 2010
SOURCE
British Journal of Cancer;10/12/2010, Vol. 103 Issue 8, p1255
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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.
ACCESSION #
54383984

 

Related Articles

  • LIM-class homeobox gene Lim1, a novel oncogene in human renal cell carcinoma. Dormoy, V; Béraud, C; Lindner, V; Thomas, L; Coquard, C; Barthelmebs, M; Jacqmin, D; Lang, H; Massfelder, T // Oncogene;4/14/2011, Vol. 30 Issue 15, p1753 

    Human clear cell renal cell carcinoma (CCC) remains resistant to therapies. The transcription factor LIM-class homeobox gene Lim1 is required for normal organogenesis, including nephrogenesis, by regulating cell movements, differentiation and growth. Its expression is controlled partly by the...

  • Differential expression of miRNA patterns in renal cell carcinoma and nontumorous tissues. Zhengjun Yi; Yurong Fu; Shushu Zhao; Xuguang Zhang; Chuanxiang Ma // Journal of Cancer Research & Clinical Oncology;Jun2010, Vol. 136 Issue 6, p855 

    MiRNAs are short single stranded RNAs that are associated with gene regulation at the transcriptional and translational level. Changes in their expression were found in a variety of human cancers. In the present study, we aimed to investigate expression profiles of miRNA (miRNA) in the clear...

  • Microarray-based identification of CUB-domain containing protein 1 as a potential prognostic marker in conventional renal cell carcinoma. Awakura, Yasuo; Nakamura, Eijiro; Takahashi, Takeshi; Kotani, Hirokazu; Mikami, Yoshiki; Kadowaki, Tadashi; Myoumoto, Akira; Akiyama, Hideo; Ito, Noriyuki; Kamoto, Toshiyuki; Manabe, Toshiaki; Nobumasa, Hitoshi; Tsujimoto, Gozoh; Ogawa, Osamu // Journal of Cancer Research & Clinical Oncology;Dec2008, Vol. 134 Issue 12, p1363 

    Renal cell carcinoma (RCC) is characterized by a variable and unpredictable clinical course. Thus, accurate prediction of the prognosis is important in clinical settings. We conducted microarray-based study to identify a novel prognostic marker in conventional RCC. The present study included the...

  • Prognostic Value of nm23 Protein Expression in Renal Cell Carcinomas. Nakagawa, Yoshinori; Tsumatani, Kenichi; Kurumatani, Norio; Cho, Masaki; Kitahori, Yoshiteru; Konishi, Noboru; Ozono, Seiichiro; Okajima, Eigoro; Hirao, Yoshihiko; Hiasa, Yoshio // Oncology;1998, Vol. 55 Issue 4, p370 

    In the present study, an analysis of whether expression of nm23-H1 and nm23-H2 proteins has prognostic significance was performed. A series of 95 renal cell carcinomas was analyzed for nuclear grade, tumor size (larger than 50 mm or not), staging in the Robson system and expression of nm23-H1...

  • MicroRNA Expression Profiling in Clear Cell Renal Cell Carcinoma: Identification and Functional Validation of Key miRNAs. He, Haowei; Wang, Linhui; Zhou, Wenquan; Zhang, Zhengyu; Wang, Longxin; Xu, Song; Wang, Dong; Dong, Jie; Tang, Chaopeng; Tang, Hao; Yi, Xiaoming; Ge, Jingping // PLoS ONE;May2015, Vol. 10 Issue 5, p1 

    Objective: This study aims to profile dysregulated microRNA (miRNA) expression in clear cell renal cell carcinoma (ccRCC) and to identify key regulatory miRNAs in ccRCC. Methods and Results: miRNA expression profiles in nine pairs of ccRCC tumor samples at three different stages and the...

  • Comparisons of three polyethyleneimine-derived nanoparticles as a gene therapy delivery system for renal cell carcinoma. Zhizhong Xu; Guobo Shen; Xiangying Xia; Xinyu Zhao; Peng Zhang; Huanhuan Wu; Qingfa Guo; Zhiyong Qian; Yuquan Wei; Shufang Liang // Journal of Translational Medicine;2010 Supplement 1, Vol. 9 Issue Suppl 1, p46 

    Background: Polyethyleneimine (PEI), which can interact with negatively charged DNA through electrostatic interaction to form nanocomplexes, has been widely attempted to use as a gene delivery system. However, PEI has some defects that are not fit for keeping on gene expression. Therefore, some...

  • Protein Expression of ZEB2 in Renal Cell Carcinoma and Its Prognostic Significance in Patient Survival Fang, Yong; Wei, Jinhuan; Cao, Jiazheng; Zhao, Hongwei; Liao, Bing; Qiu, Shaopeng; Wang, Daohu; Luo, Junhang; Chen, Wei // PLoS ONE;May2013, Vol. 8 Issue 5, p1 

    Background: ZEB2 has been reportedly shown to mediate the epithelial-to-mesenchymal transition (EMT) and disease aggressiveness in human tumors. However, the expression status of ZEB2 in renal cell carcinoma (RCC) and ZEB2’s clinicopathologic/prognostic significance are poorly understood....

  • Primary Hydatid Cyst of the Kidney in a 10 Year Old Boy. Tehranchi, Ali; Mohammadi Bukani, Hamid; Modabberi Delshad, Ali; Hamedanchi, Sepehr // Urology Journal;Summer2013, Vol. 10 Issue 3, p1004 

    The article presents a case of study a 10-year old boy, living in a rural environment, who was presented to hospital with chief complaint of dull pain in left loin and lower abdomen. He had no history of urinary tract infection, hematuria or hydatiduria. Preoperative differential diagnoses...

  • MicroRNA profile: a promising ancillary tool for accurate renal cell tumour diagnosis. Silva-Santos, R M; Costa-Pinheiro, P; Luis, A; Antunes, L; Lobo, F; Oliveira, J; Henrique, R; Jerónimo, C // British Journal of Cancer;11/12/2013, Vol. 109 Issue 10, p2646 

    Background:Renal cell tumours (RCTs) are clinically, morphologically and genetically heterogeneous. Accurate identification of renal cell carcinomas (RCCs) and its discrimination from normal tissue and benign tumours is mandatory. We, thus, aimed to define a panel of microRNAs that might aid in...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics