| Attributes | Values |
|---|
| rdf:type
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| rdfs:seeAlso
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| 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. (en)
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| 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 (en)
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| 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 (en)
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| skos:notation
| - RIV/00209805:_____/12:#0000288!RIV13-MSM-00209805
|
| http://linked.open...avai/riv/aktivita
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| http://linked.open...avai/riv/aktivity
| - P(ED2.1.00/03.0101), P(GAP301/10/1615), P(GAP301/11/1678), P(NS9812)
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
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| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
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| http://linked.open...ai/riv/idVysledku
| - RIV/00209805:_____/12:#0000288
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| http://linked.open...riv/jazykVysledku
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| http://linked.open.../riv/klicovaSlova
| - Monoclonal antibody; AGR3; AGR2; p53; Endoplasmic reticulum; Ovarian cancer; Oestrogen (en)
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| http://linked.open.../riv/klicoveSlovo
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| http://linked.open...odStatuVydavatele
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| http://linked.open...ontrolniKodProRIV
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| http://linked.open...i/riv/nazevZdroje
| - Journal of immunological methods
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| http://linked.open...in/vavai/riv/obor
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| http://linked.open...ichTvurcuVysledku
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| http://linked.open...cetTvurcuVysledku
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| http://linked.open...vavai/riv/projekt
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| http://linked.open...UplatneniVysledku
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| http://linked.open...v/svazekPeriodika
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| http://linked.open...iv/tvurceVysledku
| - Hrstka, Roman
- Vojtěšek, Bořivoj
- Nenutil, Rudolf
- Bouchalová, Pavla
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| http://linked.open...ain/vavai/riv/wos
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| issn
| |
| number of pages
| |
| http://bibframe.org/vocab/doi
| - 10.1016/j.jim.2012.01.013
|
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