ArticleProceedings of the National Academy of Sciences of the United States of America2014
MACROD2 overexpression mediates estrogen independent growth and tamoxifen resistance in breast cancers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
- Congenital heart disease risk loci identified by genome-wide association study in European patients.The Journal of clinical investigation · 2021Trial
- The Expanding Landscape of ADP-Ribosylation: Protein, DNA, RNA, and Mitochondrial Regulation.Chemical research in toxicology · 2026Review
- Drug resistance and tumor heterogeneity: cells and ensembles.Biophysical reviews · 2025Review
- Prognostic and immunotherapeutic potential of disulfidptosis-associated signature in pancreatic cancer.Frontiers in immunology · 2025Article
- Enhancing Genomic Prediction Accuracy for Body Conformation Traits in Korean Holstein Cattle.Animals : an open access journal from MDPI · 2024Article
- Human papillomavirus (HPV) integration signature in cervical lesions: identification of MACROD2 gene as HPV hot spot integration site.Archives of gynecology and obstetrics · 2023Article
- Analysis of transcriptional changes in the immune system associated with pubertal development in a longitudinal cohort of children with asthma.Nature communications · 2023Article
- Association of the MACROD2 rs6110695 A>G polymorphism with an increasing WBC count in a Korean population.Immunity, inflammation and disease · 2022Article
- Identification of sex-specific genetic associations in response to opioid analgesics in a White, non-Hispanic cohort from Southeast Minnesota.The pharmacogenomics journal · 2022Article
- Genome-wide DNA methylation profiling in chronic lymphocytic leukaemia.Frontiers in genetics · 2022Article
- Lnc-DC promotes estrogen independent growth and tamoxifen resistance in breast cancer.Cell death & disease · 2021Article
- ADP-Ribosylation as Post-Translational Modification of Proteins: Use of Inhibitors in Cancer Control.International journal of molecular sciences · 2021Review
- Regulation of tamoxifen sensitivity by the PLAC8/MAPK pathway axis is antagonized by curcumin-induced protein stability change.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Analysis of HPV Integrations in Mexican Pre-Tumoral Cervical Lesions Reveal Centromere-Enriched Breakpoints and Abundant Unspecific HPV Regions.International journal of molecular sciences · 2021Article
- Behavioural Characterisation ofCells · 2021Article
- Comparative analysis of MACROD1, MACROD2 and TARG1 expression, localisation and interactome.Scientific reports · 2020Article
- The Controversial Roles of ADP-Ribosyl Hydrolases MACROD1, MACROD2 and TARG1 in Carcinogenesis.Cancers · 2020Review
- (ADP-ribosyl)hydrolases: structure, function, and biology.Genes & development · 2020Review
- MACROD2 deficiency promotes hepatocellular carcinoma growth and metastasis by activating GSK-3β/β-catenin signaling.NPJ genomic medicine · 2020Article
- The peptide PROTAC modality: a novel strategy for targeted protein ubiquitination.Theranostics · 2020Review
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
Tamoxifen is effective for treating estrogen receptor-alpha (ER) positive breast cancers. However, few molecular mediators of tamoxifen resistance have been elucidated. Here we describe a previously unidentified gene, MACROD2 that confers tamoxifen resistance and estrogen independent growth. We found MACROD2 is amplified and overexpressed in metastatic tamoxifen-resistant tumors. Transgene overexpression of MACROD2 in breast cancer cell lines results in tamoxifen resistance, whereas RNAi-mediated gene knock down reverses this phenotype. MACROD2 overexpression also leads to estrogen independent growth in xenograft assays. Mechanistically, MACROD2 increases p300 binding to estrogen response elements in a subset of ER regulated genes. Primary breast cancers and matched metastases demonstrate MACROD2 expression can change with disease evolution, and increased expression and amplification of MACROD2 in primary tumors is associated with worse overall survival. These studies establish MACROD2 as a key mediator of estrogen independent growth and tamoxifen resistance, as well as a potential novel target for diagnostics and therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.