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Mechanisms activating A3A and fueling mutagenesis remain unclear. This study identifies determinants of basal A3A mRNA levels: basal transcript abundance tracks A3A protein and predicts APOBEC signature mutations across breast cancer cell lines. ERBB2 expression changes can raise A3A mRNA, and A3A co-expression patterns link it to viral restriction and interferon responses. Yet STAT perturbation has limited effects, while single-cell RNA-seq shows highest A3A in infiltrating immune cells. ATAC-seq and promoter analysis reveal Rel-A and Bach1 sites that elevate basal A3A expression, suggesting a complex transcriptional program.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/her2-amplification-rel-a-and-bach1-can-influence-apobec3a-expression-in-breast-cancer-cells/330790/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/her2-amplification-rel-a-and-bach1-can-influence-apobec3a-expression-in-breast-cancer-cells/330790.png","ImageObject",300,407,{"name":92,"@type":93},"Hazel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main focus of this research?","Question",{"text":112,"@type":113},"The study examines how Her2 (ERBB2), Rel-A, and Bach1 influence basal APOBEC3A (A3A) expression and APOBEC signature mutations in breast cancer cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do basal A3A mRNA levels relate to cancer mutagenesis?",{"text":117,"@type":113},"Basal A3A mRNA correlates with A3A protein levels and predicts the amount of APOBEC signature mutations across a panel of breast cancer cell lines.",{"name":119,"@type":110,"acceptedAnswer":120},"What did the study find about STAT signaling and A3A abundance?",{"text":121,"@type":113},"Reducing STAT signaling with inhibitors or shRNA produced only minor changes in A3A abundance, suggesting STAT correlations in primary tumors may reflect immune infiltration rather than direct control of A3A in cancer cells.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},330790,1790218026,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":31,"preview_page_count":4},137441390410,"https://ap-avatar.wpscdn.com/avatar/2000252f4ab5702993?_k=1776741390130283984","PLOS GENETICS  \nOPEN ACCESS  \nCitation: Dennis M, Hurley A, Bray N, Cordero C, Ilagan J, Mertz TM, et al. (2024) Her2 amplification, Rel-A, and Bach1 can influence APOBEC3A expression in breast cancer cells. PLoS Genet 20(5): e1011293 . [https://doi.org/10.1371/journal](https://doi.org/10.1371/journal). pgen.1011293  \nEditor: Ashok Bhagwat, Wayne State University, UNITED STATES  \nReceived: May 12, 2023  \nAccepted: May 8, 2024  \nPublished: May 28, 2024  \nCopyright: © 2024 Dennis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.  \nData Availability Statement: The data used in this study is openly available at the following locations: RNA-seq values for primary breast cancers was obtained from [https://gdac.broadinstitute.org/runs/](https://gdac.broadinstitute.org/runs/)[ ](https://gdac.broadinstitute.org/runs/)[stddata__2016_01_28/data/BRCA/20160128/file=](stddata__2016_01_28/data/BRCA/20160128/file=)[ ](stddata__2016_01_28/data/BRCA/20160128/file=)[gdac.broadinstitute.org_BRCA.Merge_rnaseqv2__](gdac.broadinstitute.org_BRCA.Merge_rnaseqv2__)[illuminahiseq_rnaseqv2__unc_edu__Level___](illuminahiseq_rnaseqv2__unc_edu__Level___)[RSEM_genes_normalized__data.Level_3.](RSEM_genes_normalized__data.Level_3.)[ ](RSEM_genes_normalized__data.Level_3.)[2016012800.0.0.tar.gz](2016012800.0.0.tar.gz. Mutation and RNA-seq)[. Mutation and RNA-seq](2016012800.0.0.tar.gz. Mutation and RNA-seq)[ ](2016012800.0.0.tar.gz. Mutation and RNA-seq)expression data from breast cancer cell lines was obtained from the Cancer Cell Line Encyclopedia ([https://sites.broadinstitute.org/ccle](https://sites.broadinstitute.org/ccle)) at link [https://](https://)  \nRESEARCH ARTICLE  \nHer2 amplification, Rel-A, and Bach1 can influence APOBEC3A expression in breast cancer cells  \nMadeline Dennis1, Alyssa Hurley2, Nicholas Bray1, Cameron Cordero1,2, Jose Ilagan1, Tony M. Mertz1,2, Steven A. Roberts1,2 *  \n1 School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, United States of America, 2 Department of Microbiology and Molecular Genetics, University of Vermont Cancer Center, University of Vermont, Burlington, Vermont, United States of America  \n* [steven.roberts2@wsu.edu](steven.roberts2@wsu.edu), [srober23@med.uvm.edu](srober23@med.uvm.edu)  \nAbstract  \nAPOBEC-induced mutations occur in 50% of sequenced human tumors, with APOBEC3A (A3A) being a major contributor to mutagenesis in breast cancer cells. The mechanisms that cause A3A activation and mutagenesis in breast cancers are still unknown. Here, we describe factors that influence basal A3A mRNA transcript levels in breast cancer cells. We found that basal A3A mRNA correlates with A3A protein levels and predicts the amount of APOBEC signature mutations in a panel of breast cancer cell lines, indicating that increased basal transcription may be one mechanism leading to breast cancer mutagenesis. We also show that alteration of ERBB2 expression can drive A3A mRNA levels, suggesting the enrichment of the APOBEC mutation signature in Her2-enriched breast cancer could in part result from elevated A3A transcription. Hierarchical clustering of transcripts in primary breast cancers determined that A3A mRNA was co-expressed with other genes functioning in viral restriction and interferon responses. However, reduction of STAT signaling via inhibitors or shRNA in breast cancer cell lines had only minor impact on A3A abundance. Analysis of single cell RNA-seq from primary tumors indicated that A3A mRNA was highest in infiltrating immune cells within the tumor, indicating that correlations of A3A with STAT signaling in primary tumors may be result from higher immune infiltrates and are not reflective of STAT signaling controlling A3A expression in breast cancer cells. Analysis ","cbCaivjVQ5heBgbC","https://ap.wps.com/l/cbCaivjVQ5heBgbC","pdf",2807803,"English","# Abstract\n## Mechanisms of APOBEC3A activation\n## Relationship between A3A mRNA and mutagenesis\n## Roles of ERBB2, STAT signaling, and immune infiltrates\n## Transcription factor sites regulating A3A expression","[{\"question\":\"What is the main focus of this research?\",\"answer\":\"The study examines how Her2 (ERBB2), Rel-A, and Bach1 influence basal APOBEC3A (A3A) expression and APOBEC signature mutations in breast cancer cells.\"},{\"question\":\"How do basal A3A mRNA levels relate to cancer mutagenesis?\",\"answer\":\"Basal A3A mRNA correlates with A3A protein levels and predicts the amount of APOBEC signature mutations across a panel of breast cancer cell lines.\"},{\"question\":\"What did the study find about STAT signaling and A3A abundance?\",\"answer\":\"Reducing STAT signaling with inhibitors or shRNA produced only minor changes in A3A abundance, suggesting STAT correlations in primary tumors may reflect immune infiltration rather than direct control of A3A in cancer cells.\"}]","Her2 amplification, Rel-A, and Bach1 can influence APOBEC3A expression in breast cancer cells | PDF",1789990134]