% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Dreidax:119889,
author = {D. Dreidax$^*$ and S. Bannert$^*$ and K.-O. Henrich$^*$ and
C. Schröder$^*$ and S. Bender$^*$ and C. C. Oakes$^*$ and
S. Lindner and J. H. Schulte and D. Duffy and T. Schwarzl
and M. Saadati$^*$ and V. Ehemann and A. Benner$^*$ and S.
Pfister$^*$ and M. Fischer and F. Westermann$^*$},
title = {p19-{INK}4d inhibits neuroblastoma cell growth, induces
differentiation and is hypermethylated and downregulated in
{MYCN}-amplified neuroblastomas.},
journal = {Human molecular genetics},
volume = {23},
number = {25},
issn = {1460-2083},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DKFZ-2017-00480},
pages = {6826 - 6837},
year = {2014},
abstract = {Uncontrolled cell cycle entry, resulting from deregulated
CDK-RB1-E2F pathway activity, is a crucial determinant of
neuroblastoma cell malignancy. Here we identify
neuroblastoma-suppressive functions of the p19-INK4d CDK
inhibitor and uncover mechanisms of its repression in
high-risk neuroblastomas. Reduced p19-INK4d expression was
associated with poor event-free and overall survival and
neuroblastoma risk factors including amplified MYCN in a set
of 478 primary neuroblastomas. High MYCN expression
repressed p19-INK4d mRNA and protein levels in different
neuroblastoma cell models with conditional MYCN expression.
MassARRAY and 450K methylation analyses of 105 primary
neuroblastomas uncovered a differentially methylated region
within p19-INK4d. Hypermethylation of this region was
associated with reduced p19-INK4d expression. In accordance,
p19-INK4d expression was activated upon treatment with the
demethylating agent, 2'-deoxy-5-azacytidine, in
neuroblastoma cell lines. Ectopic p19-INK4d expression
decreased viability, clonogenicity and the capacity for
anchorage-independent growth of neuroblastoma cells, and
shifted the cell cycle towards the G1/0 phase. p19-INK4d
also induced neurite-like processes and markers of neuronal
differentiation. Moreover, neuroblastoma cell
differentiation, induced by all-trans retinoic acid or
NGF-NTRK1-signaling, activated p19-INK4d expression. Our
findings pinpoint p19-INK4d as a neuroblastoma suppressor
and provide evidence for MYCN-mediated repression and for
epigenetic silencing of p19-INK4d by DNA hypermethylation in
high-risk neuroblastomas.},
keywords = {Antimetabolites, Antineoplastic (NLM Chemicals) / CDKN2D
protein, human (NLM Chemicals) / Cyclin-Dependent Kinase
Inhibitor p19 (NLM Chemicals) / MYCN protein, human (NLM
Chemicals) / N-Myc Proto-Oncogene Protein (NLM Chemicals) /
Nuclear Proteins (NLM Chemicals) / Oncogene Proteins (NLM
Chemicals) / Tretinoin (NLM Chemicals) / decitabine (NLM
Chemicals) / Azacitidine (NLM Chemicals)},
cin = {C010 / C060 / B062 / B087},
ddc = {570},
cid = {I:(DE-He78)C010-20160331 / I:(DE-He78)C060-20160331 /
I:(DE-He78)B062-20160331 / I:(DE-He78)B087-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25104850},
doi = {10.1093/hmg/ddu406},
url = {https://inrepo02.dkfz.de/record/119889},
}