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Title
The functional role(s) of eukaryotic pre-replication complex elements in glioblastoma multiforme pathogenesis / submitted by Erdogan Pekcan Erkan
Additional Titles
The functional role(s) of eukaryotic pre-replication complex elements in glioblastoma multiforme pathogenesis
AuthorErkan, Erdogan Pekcan
CensorSaydam, Okay
Published2013
Description65 Bl. : Ill., graph. Darst.
Institutional NoteWien, Med. Univ., Diss., 2013
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Abweichender Titel laut Übersetzung der Verfasserin/des Verfassers
Zsfassung in dt. Sprache
LanguageEnglish
Bibl. ReferenceOeBB
Document typeDissertation (PhD)
Keywords (DE)Glioblastoma multiforme / minichromosome maintenance / MCM7 / TCGA / prognostischer Marker
Keywords (EN)Glioblastoma multiforme / minichromosome maintenance / MCM7 / TCGA / prognostic marker
URNurn:nbn:at:at-ubmuw:1-5570 Persistent Identifier (URN)
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 The work is publicly available
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The functional role(s) of eukaryotic pre-replication complex elements in glioblastoma multiforme pathogenesis [2.41 mb]
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Abstract (German)

Minichromosome maintenance (MCM) Proteine sind Schlüsselelemente, die als ein Teil des Präreplikationkomplexes fungieren indem sie die DNA Replikation in Eukaryoten starten. Aufgrund dieser wichtigen Rolle, ließ sich die Überexpression der MCM Proteine in einigen bösartigen Tumoren nachweisen. Das Ziel dieser Studie war, die funktionelle Rolle der MCM Proteine in der Glioblastoma Multiforme (GBM) Pathogenese zu identifizieren.

Mittels Expressionsanalysen durch Quantitative real-time PCR (qRT-PCR) wurde gezeigt, dass MCM2-7 mRNA in GBM verglichen zu normaler, weißer Hirnsubstanz (NWM) signifikant hochreguliert ist. Weiters zeigten immunohistochemische Färbungen, dass MCM2, MCM5 und MCM7 Proteine im Vergleich zu Grad II, Grad III und NWM signifikant hochreguliert sind.

Transiente und stabile Ausschaltung von MCM7 resultierte in einer reduzierten Zellproliferation, und inhibierte GBM Tumorwachstum im Xenotransplantat als auch im orthotopischen Mausmodell.

Diese Daten legen nahe, dass MCM7 als prognostischer Marker und als neuer therapeutisches Ziel in der GBM Therapie verwendet werden kann.

Abstract (English)

Minichromosome maintenance (MCM) proteins are key elements that function as a part of the pre-replication complex to initiate DNA replication in eukaryotes. Consistent with their roles in initiating DNA replication, overexpression of MCM family members have been observed in several malignancies. The aim of this study was to identify the functional role(s) of MCM proteins in Glioblastoma Multiforme (GBM) pathogenesis.

Quantitative real-time PCR (qRT-PCR)-based expression profiling showed that MCM2-7 mRNAs were significantly upregulated in GBM compared to normal white matter (NWM). Moreover, immunohistochemical staining studies showed that MCM2, MCM5 and MCM7 proteins were significantly upregulated in human GBM tumor tissues, compared to Grade II, Grade III and NWM tissues. Transient and stable knockdown of MCM7 resulted in reduced cell proliferation, and also inhibited GBM tumor growth both in xenograft and orthotopic in mouse models.

The present data suggest that MCM7 can be used as prognostic marker and served as a novel therapeutic target in GBM therapy.

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