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Overexpression of f...
Overexpression of full-length ETV1 transcripts in clinical prostate cancer due to gene translocation.
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- Gasi, Delila, 1982 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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van der Korput, Hetty A (författare)
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Douben, Hannie C (författare)
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de Klein, Annelies (författare)
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de Ridder, Corrina M (författare)
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van Weerden, Wytske M (författare)
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Trapman, Jan (författare)
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(creator_code:org_t)
- 2011-01-26
- 2011
- Engelska.
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 6:1
- Relaterad länk:
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https://journals.plo...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- ETV1 is overexpressed in a subset of clinical prostate cancers as a fusion transcript with many different partners. However, ETV1 can also be overexpressed as a full-length transcript. Full-length ETV1 protein functions differently from truncated ETV1 produced by fusion genes. In this study we describe the genetic background of full-length ETV1 overexpression and the biological properties of different full-length ETV1 isoforms in prostate cancer. Break-apart FISH showed in five out of six patient samples with overexpression of full-length ETV1 a genomic rearrangement of the gene, indicating frequent translocation. We were able to study the rearrangements in more detail in two tumors. In the first tumor 5'-RACE on cDNA showed linkage of the complete ETV1 transcript to the first exon of a prostate-specific two exon ncRNA gene that maps on chromosome 14 (EST14). This resulted in the expression of both full-length ETV1 transcripts and EST14-ETV1 fusion transcripts. In chromosome spreads of a xenograft derived from the second prostate cancer we observed a complex ETV1 translocation involving a chromosome 7 fragment that harbors ETV1 and fragments of chromosomes 4 and 10. Further studies revealed the overexpression of several different full-length transcripts, giving rise to four protein isoforms with different N-terminal regions. Even the shortest isoform synthesized by full-length ETV1 stimulated in vitro anchorage-independent growth of PNT2C2 prostate cells. This contrasts the lack of activity of even shorter N-truncated ETV1 produced by fusion transcripts. Our findings that in clinical prostate cancer overexpression of full-length ETV1 is due to genomic rearrangements involving different chromosomes and the identification of a shortened biologically active ETV1 isoform are highly relevant for understanding the mechanism of ETV1 function in prostate cancer.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Nyckelord
- Chromosomes
- Human
- DNA-Binding Proteins
- genetics
- Gene Expression Regulation
- Neoplastic
- Humans
- Male
- Prostatic Neoplasms
- genetics
- Protein Isoforms
- RNA
- Neoplasm
- analysis
- Transcription Factors
- genetics
- Translocation
- Genetic
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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