Anterior Gradient-3: A novel biomarker for ovarian cancer that mediates cisplatin resistance in xenograft models

Gray, Terry A.; MacLaine, Nicola J.; Michie, Caroline O.; Bouchalová, Pavla; Murray, Euan; Howie, J. W.; Hrstka, Roman; Maslon, Magdalena M.; Nenutil, Rudolf; Vojtesek, Borek; Langdon, Simon P.; Hayward, Larry; Gourley, Charlie; Hupp, Ted R.

doi:10.1016/j.jim.2012.01.013

Cited by 43 publications

(69 citation statements)

References 53 publications

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“…However, ovarian cancer studies have highlighted a situation in which agr3 can sometimes dominate over agr2. Using monoclonal antibodies directed towards AGR3, ovarian cancers can produce AGR3 and/or AGR2 protein providing a novel model to study how these two contiguous genes can be uncoupled in their expression [55]. Consistent with this study, agr3 was found expressed in serous ovarian tumours [72], however, the protein appears to be more homogeneously expressed in mucinous ovarian tumours [55].…”

Section: Agr2 Gene and Protein Expression In Relation To Cancer Cell supporting

confidence: 76%

“…This would suggest that patient drug resistance could be predicted based on high expression of the AGR2 pathway. Animal studies have shown the agr2 or agr3 gene can mediate cisplatin resistance in cancer cell xenografts [55] [53]. Engineering a cell line that produces AGR2 protein highlights it is able to induce mucins, increase cell proliferation, and attenuate the p53 response to cisplatin [11].…”

Section: Agr2 Gene and Protein Expression In Relation To Cancer Cell mentioning

confidence: 99%

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Mechanisms of anterior gradient-2 regulation and function in cancer

Brychtová

Mohtar

Vojtěšek

et al. 2015

Seminars in Cancer Biology

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Section: Agr2 Gene and Protein Expression In Relation To Cancer Cell supporting

confidence: 76%

Section: Agr2 Gene and Protein Expression In Relation To Cancer Cell mentioning

confidence: 99%

Mechanisms of anterior gradient-2 regulation and function in cancer

Brychtová

Mohtar

Vojtěšek

et al. 2015

Seminars in Cancer Biology

Self Cite

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“…AGR genes, a protein disulfide isomerase (PDI) family, harbour core thioredoxin folds (CxxS motifs) that have the potential to regulate protein folding and maturation. AGR3 is overexpressed by a hormone (estrogen-receptor α)-independent mechanism, identifying a novel protein-folding associated pathway that can mediate resistance to DNA-damaging agents in human cancers (17). These findings indicate that the downregulation of AGR3 by 15d-PGJ 2 may cause DNA-damage, leading to the apoptosis of endometrial cancer cells.…”

Section: Discussionmentioning

confidence: 88%

15-Deoxy-Δ12,14-prostaglandin J2 induces growth inhibition, cell cycle arrest and apoptosis in human endometrial cancer cell lines

Narahara

2013

International Journal of Molecular Medicine

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Abstract. 15-Deoxy-∆ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), a peroxisome proliferator-activated receptor γ ligand, has been reported to have antiproliferative activity in certain types of cancer. The purpose of this study was to elucidate the effect of 15d-PGJ 2 on endometrial cancer cells, as well as the mechanism of action. Endometrial cancer-derived cells (HHUA, Ishikawa and HEC-59) were treated with various concentrations of 15d-PGJ 2 , and its effects on cell growth, the cell cycle and apoptosis were investigated in vitro. Using cDNA microarrays, some potential targets of this drug were identified. All endometrial cancer cell lines were sensitive to the growth-inhibitory effect of 15d-PGJ 2 . Cell cycle arrest at the G2/M phase of the cell cycle and induction of apoptosis were observed. Concerning the gene expression changes induced by 15d-PGJ 2 treatment, the upregulation of aldo-keto reductase family 1 member C3 (AKR1C3) and the downregulation of anterior gradient homolog 3 (AGR3) and nitric oxide synthase 2A (NOS2A) were confirmed using western blot analysis in all the cell lines examined. These results suggest that 15d-PGJ 2 may be a novel therapeutic option for the treatment of endometrial cancer.

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“…65 AGR3 is overexpressed in breast cancer, and expression of AGR2 and AGR3 correlates with estrogen expression. 66 However, estrogen-independent expression of AGR2 and AGR3 has also been observed in prostate, pancreatic, esophageal, and ovarian cancers. 66,67 When the ERBB2-subtype expression profile was compared with that of the ER/PR-positive group, we identified underexpression of ESR1 and TFF1.…”

mentioning

confidence: 99%

“…66 However, estrogen-independent expression of AGR2 and AGR3 has also been observed in prostate, pancreatic, esophageal, and ovarian cancers. 66,67 When the ERBB2-subtype expression profile was compared with that of the ER/PR-positive group, we identified underexpression of ESR1 and TFF1. TFF1 is an ER-responsive gene co-expressed with TFF3 as components of a luminal epithelial signature in breast cancer cells.…”

mentioning

confidence: 99%