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Statements

Subject Item
n2:RIV%2F00209805%3A_____%2F12%3A%230000288%21RIV13-MSM-00209805
rdf:type
skos:Concept n12:Vysledek
rdfs:seeAlso
http://www.sciencedirect.com/science/article/pii/S002217591200035X
dcterms:description
The Anterior Gradient genes AGR2 and AGR3 are part of Protein Disulfide Isomerase (PDI) family and harbour core thioredoxin folds (CxxS motifs) that have the potential to regulate protein folding and maturation. Despite the fact that AGR2 and AGR3 genes are contiguous on chromosome 7p21.1-3, AGR3 protein has rarely been identified along with AGR2 protein. Therefore there is little information on how AGR3 protein is expressed in normal and diseased states. A panel of three monoclonal antibodies was generated towards AGR3 protein for identifying novel clinical models that can be used to define whether AGR3 protein could play a positive or negative role in human cancer development. One monoclonal antibody was AGR3-specific and bound a linear epitope that could be defined using both pep-scan and phage-peptide library screening. Using this antibody, endogenous AGR3 protein expression was shown to be cytosolic in four human ovarian cancer subtypes; serous, endometrioid, clear cell, and mucinous. Mucinous ovarian cancers produced the highest number of AGR3 positive cells. AGR3 expression is coupled to AGR2 expression only in mucinous ovarian cancers, whereas AGR3 and AGR2 expressions are uncoupled in the other three types of ovarian cancer. AGR3 expression in ovarian cancer is independent of oestrogen-receptor expression, which is distinct from the oestrogen-receptor dependent expression of AGR3 in breast cancers. Isogenic cancer cell models were created that overexpress AGR3 and these demonstrated that AGR3 mediates cisplatin-resistance in mouse xenografts. These data indicate that AGR3 is over-expressed by a hormone (oestrogen-receptor α)-independent mechanism and identify a novel protein-folding associated pathway that could mediate resistance to DNA-damaging agents in human cancers. The Anterior Gradient genes AGR2 and AGR3 are part of Protein Disulfide Isomerase (PDI) family and harbour core thioredoxin folds (CxxS motifs) that have the potential to regulate protein folding and maturation. Despite the fact that AGR2 and AGR3 genes are contiguous on chromosome 7p21.1-3, AGR3 protein has rarely been identified along with AGR2 protein. Therefore there is little information on how AGR3 protein is expressed in normal and diseased states. A panel of three monoclonal antibodies was generated towards AGR3 protein for identifying novel clinical models that can be used to define whether AGR3 protein could play a positive or negative role in human cancer development. One monoclonal antibody was AGR3-specific and bound a linear epitope that could be defined using both pep-scan and phage-peptide library screening. Using this antibody, endogenous AGR3 protein expression was shown to be cytosolic in four human ovarian cancer subtypes; serous, endometrioid, clear cell, and mucinous. Mucinous ovarian cancers produced the highest number of AGR3 positive cells. AGR3 expression is coupled to AGR2 expression only in mucinous ovarian cancers, whereas AGR3 and AGR2 expressions are uncoupled in the other three types of ovarian cancer. AGR3 expression in ovarian cancer is independent of oestrogen-receptor expression, which is distinct from the oestrogen-receptor dependent expression of AGR3 in breast cancers. Isogenic cancer cell models were created that overexpress AGR3 and these demonstrated that AGR3 mediates cisplatin-resistance in mouse xenografts. These data indicate that AGR3 is over-expressed by a hormone (oestrogen-receptor α)-independent mechanism and identify a novel protein-folding associated pathway that could mediate resistance to DNA-damaging agents in human cancers.
dcterms:title
Anterior Gradient-3: a novel biomarker for ovarian cancer that mediates cisplatin resistance in xenograft models Anterior Gradient-3: a novel biomarker for ovarian cancer that mediates cisplatin resistance in xenograft models
skos:prefLabel
Anterior Gradient-3: a novel biomarker for ovarian cancer that mediates cisplatin resistance in xenograft models Anterior Gradient-3: a novel biomarker for ovarian cancer that mediates cisplatin resistance in xenograft models
skos:notation
RIV/00209805:_____/12:#0000288!RIV13-MSM-00209805
n3:aktivita
n16:P
n3:aktivity
P(ED2.1.00/03.0101), P(GAP301/10/1615), P(GAP301/11/1678), P(NS9812)
n3:cisloPeriodika
1-2
n3:dodaniDat
n9:2013
n3:domaciTvurceVysledku
n8:1267728 n8:5713021 n8:1330586 n8:9637419
n3:druhVysledku
n14:J
n3:duvernostUdaju
n17:S
n3:entitaPredkladatele
n15:predkladatel
n3:idSjednocenehoVysledku
122868
n3:idVysledku
RIV/00209805:_____/12:#0000288
n3:jazykVysledku
n10:eng
n3:klicovaSlova
Monoclonal antibody; AGR3; AGR2; p53; Endoplasmic reticulum; Ovarian cancer; Oestrogen
n3:klicoveSlovo
n5:p53 n5:AGR2 n5:Monoclonal%20antibody n5:Oestrogen n5:Endoplasmic%20reticulum n5:Ovarian%20cancer n5:AGR3
n3:kodStatuVydavatele
NL - Nizozemsko
n3:kontrolniKodProRIV
[54D694C0FF7B]
n3:nazevZdroje
Journal of immunological methods
n3:obor
n11:FD
n3:pocetDomacichTvurcuVysledku
4
n3:pocetTvurcuVysledku
14
n3:projekt
n13:GAP301%2F11%2F1678 n13:GAP301%2F10%2F1615 n13:NS9812 n13:ED2.1.00%2F03.0101
n3:rokUplatneniVysledku
n9:2012
n3:svazekPeriodika
378
n3:tvurceVysledku
Bouchalová, Pavla Nenutil, Rudolf Vojtěšek, Bořivoj Hrstka, Roman
n3:wos
000304285900003
s:issn
0022-1759
s:numberOfPages
13
n19:doi
10.1016/j.jim.2012.01.013