2019
DOI: 10.3390/cancers11010043
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Poly-ADP-Ribosylation of Estrogen Receptor-Alpha by PARP1 Mediates Antiestrogen Resistance in Human Breast Cancer Cells

Abstract: Therapeutic targeting of estrogen receptor-α (ERα) by the anti-estrogen tamoxifen is standard of care for premenopausal breast cancer patients and remains a key component of treatment strategies for postmenopausal patients. While tamoxifen significantly increases overall survival, tamoxifen resistance remains a major limitation despite continued expression of ERα in resistant tumors. Previous reports have described increased oxidative stress in tamoxifen resistant versus sensitive breast cancer and a role for … Show more

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Cited by 11 publications
(14 citation statements)
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“…Initial studies of ADPRylation in cancers, mainly PARylation, in cell lines and tumor specimens, have revealed significant variations in ADPRylation levels among different cancer types, as well across individual samples of a given cancer type (19,20,30,(46)(47)(48). Few studies, however, have investigated endogenous ADPRylation as a potential biomarker for responses to PARP inhibitor treatment.…”
Section: Adprylation and Sensitivity To Parp Inhibitors In Ovarian Cancersmentioning
confidence: 99%
“…Initial studies of ADPRylation in cancers, mainly PARylation, in cell lines and tumor specimens, have revealed significant variations in ADPRylation levels among different cancer types, as well across individual samples of a given cancer type (19,20,30,(46)(47)(48). Few studies, however, have investigated endogenous ADPRylation as a potential biomarker for responses to PARP inhibitor treatment.…”
Section: Adprylation and Sensitivity To Parp Inhibitors In Ovarian Cancersmentioning
confidence: 99%
“…PARP1 activates the MAPK and mTOR pathways and thus induces authophagy, resulting in the radioresistance of nasopharyngeal cancer [ 27 ]. It also PARylates the estrogen receptor α, which is associated with resistance to tamoxifen in breast cancer patients [ 18 , 28 , 29 ]. In both cases, application of PARP1 inhibitors led to the sensitisation to applied treatment [ 27 , 28 , 29 ].…”
Section: Introductionmentioning
confidence: 99%
“…Among the genes in module 1, we found PARP1 and E2F1 , recently discovered important genes for endocrine resistance in breast cancer, supporting the validity of our approach. We also found minichromosome maintenance (MCM) family genes as important genes, namely MCM2 and MCM7 , RAD51 , and TCF3 ( Figure 4 ), which yet to be thoroughly studied [ 27 29 ]. MCM family genes ( MCM2-7 ) form an MCM complex protein that functions as a DNA replication licensing factor and plays a central role in eukaryotic DNA replication [ 30 ].…”
Section: Resultsmentioning
confidence: 99%