dc.contributor.author
Kacprzyk, Lukasz A.
dc.contributor.author
Laible, Mark
dc.contributor.author
Andrasiuk, Tatjana
dc.contributor.author
Brase, Jan C.
dc.contributor.author
Börno, Stefan T.
dc.contributor.author
Fälth, Maria
dc.contributor.author
Kuner, Ruprecht
dc.contributor.author
Lehrach, Hans
dc.contributor.author
Schweiger, Michal R.
dc.contributor.author
Sültmann, Holger
dc.date.accessioned
2018-06-08T04:08:30Z
dc.date.available
2015-10-06T13:10:00.798Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/16662
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-20843
dc.description.abstract
Background Overexpression of ERG transcription factor due to genomic ERG-
rearrangements defines a separate molecular subtype of prostate tumors. One of
the consequences of ERG accumulation is modulation of the cell’s gene
expression profile. Tudor domain-containing protein 1 gene (TDRD1) was
reported to be differentially expressed between TMPRSS2:ERG-negative and
TMPRSS2:ERG-positive prostate cancer. The aim of our study was to provide a
mechanistic explanation for the transcriptional activation of TDRD1 in ERG
rearrangement-positive prostate tumors. Methodology/Principal Findings Gene
expression measurements by real-time quantitative PCR revealed a remarkable
co-expression of TDRD1 and ERG (r2 = 0.77) but not ETV1 (r2<0.01) in human
prostate cancer in vivo. DNA methylation analysis by MeDIP-Seq and bisulfite
sequencing showed that TDRD1 expression is inversely correlated with DNA
methylation at the TDRD1 promoter in vitro and in vivo (ρ = −0.57).
Accordingly, demethylation of the TDRD1 promoter in TMPRSS2:ERG-negative
prostate cancer cells by DNA methyltransferase inhibitors resulted in TDRD1
induction. By manipulation of ERG dosage through gene silencing and forced
expression we show that ERG governs loss of DNA methylation at the TDRD1
promoter-associated CpG island, leading to TDRD1 overexpression.
Conclusions/Significance We demonstrate that ERG is capable of disrupting a
tissue-specific DNA methylation pattern at the TDRD1 promoter. As a result,
TDRD1 becomes transcriptionally activated in TMPRSS2:ERG-positive prostate
cancer. Given the prevalence of ERG fusions, TDRD1 overexpression is a common
alteration in human prostate cancer which may be exploited for diagnostic or
therapeutic procedures.
en
dc.rights.uri
http://creativecommons.org/licenses/by/2.0/de/
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie
dc.title
ERG Induces Epigenetic Activation of Tudor Domain-Containing Protein 1 (TDRD1)
in ERG Rearrangement-Positive Prostate Cancer
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
PLoS ONE. - 8 (2013), 3, Artikel Nr. e59976
dcterms.bibliographicCitation.doi
10.1371/journal.pone.0059976
dcterms.bibliographicCitation.url
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059976
refubium.affiliation
Biologie, Chemie, Pharmazie
de
refubium.mycore.fudocsId
FUDOCS_document_000000023237
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000005497
dcterms.accessRights.openaire
open access