ETS transcription factors and their emerging roles in human cancer

Seth, Arun; Watson, Dennis K.

doi:10.1016/j.ejca.2005.08.013

Cited by 404 publications

(367 citation statements)

References 136 publications

Supporting

Mentioning

351

Contrasting

Unclassified

Order By: Relevance

“…The transcription factor ETS-1 was described as an important regulator of tumour angiogenesis (Wernert et al, 1992, for review see Seth and Watson, 2005). To elucidate whether a direct relation between WT1 and ETS-1 in endothelial cells might exist, we performed quantitative reverse transcription (RT)-PCR for ETS-1 on RNA from WT1-silenced and control-transfected HUVECs.…”

Section: The Ets-1 Transcription Factor Is Regulated By Wt1mentioning

confidence: 99%

“…ETS-1 belongs to the large group of ETS transcription factors, which are characterized by a conserved winged helix-turn-helix DNA-binding domain (for review see Seth and Watson, 2005). Prompted by the partial overlapping expression pattern of WT1 and ETS-1 in the tumour vessels, we reasoned that a direct relation between both transcription factors might exist.…”

Section: Wt1 Activates Ets-1 In Endothelial Cellsmentioning

confidence: 99%

“…A large variety of molecules have been described as target genes of ETS-1 (Seth and Watson, 2005). With respect to an important role in angiogenesis, we selected VEGF receptors and angiopoietins.…”

Section: Wt1 Activates Ets-1 In Endothelial Cellsmentioning

confidence: 99%

See 2 more Smart Citations

The Wilms' tumour suppressor WT1 is involved in endothelial cell proliferation and migration: expression in tumour vessels in vivo

Wagner

Schedl

et al. 2008

Oncogene

View full text Add to dashboard Cite

Vascularization is an important step in tumour growth. Although a variety of molecules, for example, VEGF, ETS-1 or nestin have been implicated in tumour angiogenesis, the molecular mechanisms of vessel formation are not fully characterized. We showed that the Wilms' tumour suppressor WT1 activates nestin during development. Here we tested whether WT1 might also be involved in tumour angiogenesis. Endothelial WT1 expression was detected in 95% of 113 tumours of different origin. To analyse the function of WT1 in endothelial cells, we used an RNAi approach in vitro and showed that inhibition of WT1 reduces cell proliferation, migration and endothelial tube formation. On a molecular level, WT1 silencing diminished expression of the ETS-1 transcription factor. WT1 and ETS-1 shared an overlapping expression in tumour endothelia. The ETS-1 promoter was stimulated approximately 10-fold by transient co-transfection of a WT1 expression construct and WT1 bound to the ETS-1 promoter in chromatin immunoprecipitation and electrophoretic mobility shift assays. Deletion of the identified WT1-binding site abolished stimulation of the ETS-1 promoter by WT1. These findings suggest that transcriptional activation of ETS-1 by the Wilms' tumour suppressor WT1 is a crucial step in tumour vascularization via regulation of endothelial cell proliferation and migration.

show abstract

Section: The Ets-1 Transcription Factor Is Regulated By Wt1mentioning

confidence: 99%

Section: Wt1 Activates Ets-1 In Endothelial Cellsmentioning

confidence: 99%

See 1 more Smart Citation

The Wilms' tumour suppressor WT1 is involved in endothelial cell proliferation and migration: expression in tumour vessels in vivo

Wagner

Schedl

et al. 2008

Oncogene

View full text Add to dashboard Cite

show abstract

“…Tomlins et al (2005) identified the overexpression of ERG (21q22.3) and ETV1 (7p21.2) in prostate cancer tumour cells after DNA fusion with a prostate-specific gene, TMPRSS2. ERG and ETV1 proteins are members of the ETS family of transcription factors, which are important in several oncogenic pathways (Watson et al, 2002;Seth and Watson, 2005). The TMPRSS2 protein is a serine protease that is highly expressed in both normal and cancerous prostate cells, and expression is regulated by androgens (Lin et al, 1999;Afar et al, 2001).…”

mentioning

confidence: 99%

Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer

et al. 2007

View full text Add to dashboard Cite

The prostate-specific gene, TMPRSS2 is fused with the gene for the transcription factor ERG in a large proportion of human prostate cancers. The prognostic significance of the presence of the TMPRSS2:ERG gene fusion product remains controversial. We examined prostate cancer specimens from 165 patients who underwent surgery for clinically localised prostate cancer between 1998 and 2006. We tested for the presence of TMPRSS2:ERG gene fusion product, using RT -PCR and direct sequencing. We conducted a survival analysis to determine the prognostic significance of the presence of the TMPRSS2:ERG fusion gene on the risk of prostate cancer recurrence, adjusting for the established prognostic factors. We discovered that the fusion gene was expressed within the prostate cancer cells in 81 of 165 (49.1%) patients. Of the 165 patients, 43 (26.1%) developed prostate-specific antigen (PSA) relapse after a mean follow-up of 28 months. The subgroup of patients with the fusion protein had a significantly higher risk of recurrence (58.4% at 5 years) than did patients who lacked the fusion protein (8.1%, Po0.0001). In a multivariable analysis, the presence of gene fusion was the single most important prognostic factor; the adjusted hazard ratio for disease recurrence for patients with the fusion protein was 8.6 (95% CI ¼ 3.6 -20.6, Po0.0001) compared to patients without the fusion protein. Among prostate cancer patients treated with surgery, the expression of TMPRSS2:ERG fusion gene is a strong prognostic factor and is independent of grade, stage and PSA level.

show abstract

“…6 In human cancers, ETS genes are frequently found amplified, overexpressed or rearranged, the latter including chimeric fusion products characteristic of Ewing's sarcoma and certain leukemias. 6 TMPRSS2, which encodes a serine protease with a transmembrane domain, 7 is highly expressed in both normal and neoplastic prostate epithelium, 8,9 and its expression in prostate cancer cells is androgen-regulated. 8,10 In prostate tumors harboring rearrangements, most frequently the non-coding first exon of TMPRSS2 has been found fused to the fourth exon of ERG in the expressed transcript.…”

mentioning

confidence: 99%

A variant TMPRSS2 isoform and ERG fusion product in prostate cancer with implications for molecular diagnosis

et al. 2007

View full text Add to dashboard Cite

Prostate cancer is the most commonly diagnosed cancer among men in the United States. Recently, fusion of TMPRSS2 with ETS family oncogenic transcription factors has been identified as a common molecular alteration in prostate cancer, where most often the rearrangement places ERG under the androgen-regulated transcriptional control of TMPRSS2. Here, we carried out rapid amplification of cDNA ends (RACE) on a prostate cancer specimen carrying an atypical aberration discovered by array-based comparative genomic hybridization (array CGH), suggesting an alternative fusion partner of ERG. We identified novel transcribed sequences fused to ERG, mapping 4 kb upstream of the TMPRSS2 start site. The sequences derive from an apparent second TMPRSS2 isoform, which we found also expressed in some prostate tumors, suggesting similar androgenregulated control. In a reverse transcription-polymerase chain reaction (RT-PCR)-based survey of 63 prostate tumor specimens (54 primary and nine lymph node metastases), 44 (70%) cases expressed either the known or novel variant TMPRSS2-ERG fusion, 28 (44%) expressed both, 10 (16%) expressed only the known, and notably six (10%) expressed only the variant isoform fusion. In this specimen set, the presence of a TMPRSS2-ERG fusion showed no statistical association with tumor stage, Gleason grade or recurrence-free survival. Nonetheless, the discovery of a novel variant TMPRSS2 isoform-ERG fusion adds to the characterization of ETS-family rearrangements in prostate cancer, and has important implications for the accurate molecular diagnosis of TMPRSS2-ETS fusions. Recently, by examining outlier values of gene expression in human cancers, Tomlins et al 5 discovered elevated expression of the ETS family members ERG (v-ets erythroblastosis virus E26 oncogene like) and ETV1 (Ets variant gene 1) to be a common feature of prostate cancer. Elevated expression resulted from chromosomal rearrangement fusing TMPRSS2 (transmembrane protease, serine 2) (chr 21q22.3) to ERG (chr 21q22.2), an apparent intra-chromosomal deletion of B3 Mb on chromosome 21, or less frequently to ETV1, an interchromosomal rearrangement between chr 21q22.3 and chr 7p21.2.

show abstract

ETS transcription factors and their emerging roles in human cancer

Cited by 404 publications

References 136 publications

The Wilms' tumour suppressor WT1 is involved in endothelial cell proliferation and migration: expression in tumour vessels in vivo

The Wilms' tumour suppressor WT1 is involved in endothelial cell proliferation and migration: expression in tumour vessels in vivo

Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer

A variant TMPRSS2 isoform and ERG fusion product in prostate cancer with implications for molecular diagnosis

Contact Info

Product

Resources

About