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Naslov:Expression analysis of all protease genes reveals cathepsin K to be overexpressed in glioblastoma
Avtorji:ID Verbovšek, Urška (Avtor)
ID Motaln, Helena (Avtor)
ID Rotter, Ana (Avtor)
ID Atai, Nadia A. (Avtor)
ID Gruden, Kristina (Avtor)
ID Noorden, Cornelis J. F. van (Avtor)
ID Lah Turnšek, Tamara (Avtor)
Datoteke:URL URL - Izvorni URL, za dostop obiščite http://dx.doi.org/10.1371/journal.pone.0111819
 
.pdf PDF - Predstavitvena datoteka, prenos (1,38 MB)
MD5: D28EC3AFE34AF51D6FBBCE1F5E5AD2F2
 
Jezik:Angleški jezik
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:Logo NIB - Nacionalni inštitut za biologijo
Povzetek:Background Cancer genome and transcriptome analyses advanced our understanding of cancer biology. We performed transcriptome analysis of all known genes of peptidases also called proteases and their endogenous inhibitors in glioblastoma multiforme (GBM), which is one of the most aggressive and deadly types of brain cancers, where unbalanced proteolysis is associated with tumor progression. Methods Comparisons were performed between the transcriptomics of primary GBM tumors and unmatched non-malignant brain tissue, and between GBM cell lines (U87-MG and U373) and a control human astrocyte cell line (NHA). Publicly-available data sets and our own datasets were integrated and normalized using bioinformatics tools to reveal protease and protease inhibitor genes with deregulated expression in both malignant versus non-malignant tissues and cells. Results Of the 311 protease genes identified to be differentially expressed in both GBM tissues and cells, 5 genes were highly overexpressed, 2 genes coding for non-peptidase homologues transferrin receptor (TFRC) and G protein-coupled receptor 56 (GPR56), as well as 3 genes coding for the proteases endoplasmic reticulum aminopeptidase 2 (ERAP2), glutamine-fructose-6-phosphate transaminase 2 (GFPT2) and cathepsin K (CTSK), whereas one gene, that of the serine protease carboxypeptidase E (CPE) was strongly reduced in expression. Seventy five protease inhibitor genes were differentially expressed, of which 3 genes were highly overexpressed, the genes coding for stefin B (CSTB), peptidase inhibitor 3 (PI3 also named elafin) and CD74. Seven out of 8 genes (except CSTB) were validated using RT-qPCR in GBM cell lines. CTSK overexpression was validated using RT-qPCR in GBM tissues as well. Cathepsin K immunohistochemical staining and western blotting showed that only proteolytically inactive proforms of cathepsin K were overexpressed in GBM tissues and cells. Conclusions The presence of high levels of inactive proforms of cathepsin K in GBM tissues and cells indicate that in GBM the proteolytic/collagenolytic role is not its primary function but it plays rather a different yet unknown role.
Ključne besede:glioblastoma multiforme, genes
Status publikacije:Objavljeno
Verzija publikacije:Objavljena publikacija
Datum objave:30.10.2014
Leto izida:2014
Št. strani:str. 1- 12
Številčenje:Vol. 9, iss. 10
PID:20.500.12556/DiRROS-20010 Novo okno
UDK:616
ISSN pri članku:1932-6203
DOI:10.1371/journal.pone.0111819 Novo okno
COBISS.SI-ID:3237711 Novo okno
Opomba:Nasl. z nasl. zaslona; Opis vira z dne 4. 11. 2014; Soavtorji: Helena Motaln, Ana Rotter, Nadia A. Atai, Kristina Gruden, Cornelis J. F. Van Noorden, Tamara T. Lah;
Datum objave v DiRROS:02.08.2024
Število ogledov:15
Število prenosov:6
Metapodatki:XML RDF-CHPDL DC-XML DC-RDF
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Gradivo je del revije

Naslov:PloS one
Založnik:Public Library of Science
ISSN:1932-6203
COBISS.SI-ID:2005896 Novo okno

Gradivo je financirano iz projekta

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:P1-0245-2009
Naslov:Ekotoksiologija, toksikološka genomika in karcinogeneza

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Licenca:CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by/4.0/deed.sl
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