{"doi":"10.1016/j.celrep.2022.111909","title":"ATM suppresses c-Myc overexpression in the mammary epithelium in response to estrogen","abstract":"ATM gene mutation carriers are predisposed to estrogen-receptor-positive breast cancer (BC). ATM prevents BC oncogenesis by activating p53 in every cell; however, much remains unknown about tissue-specific oncogenesis after ATM loss. Here, we report that ATM controls the early transcriptional response to estrogens. This response depends on topoisomerase II (TOP2), which generates TOP2-DNA double-strand break (DSB) complexes and rejoins the breaks. When TOP2-mediated ligation fails, ATM facilitates DSB repair. After estrogen exposure, TOP2-dependent DSBs arise at the c-MYC enhancer in human BC cells, and their defective repair changes the activation profile of enhancers and induces the overexpression of many genes, including the c-MYC oncogene. CRISPR/Cas9 cleavage at the enhancer also causes c-MYC overexpression, indicating that this DSB causes c-MYC overexpression. Estrogen treatment induced c-Myc protein overexpression in mammary epithelial cells of ATM-deficient mice. In conclusion, ATM suppresses the c-Myc-driven proliferative effects of estrogens, possibly explaining such tissue-specific oncogenesis.","journal":"Cell Reports","year":2022,"id":273524,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9616,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":941003,"name":"Md Rasel Al Mahmud","orcid":"0000-0003-0401-3311","position":1,"is_corresponding":false},{"id":941004,"name":"Md Maminur Rahman","orcid":"0009-0004-5700-0009","position":2,"is_corresponding":false},{"id":329462,"name":"Shunichi Takeda","orcid":"0000-0002-7924-7991","position":3,"is_corresponding":false},{"id":483350,"name":"Hiroyuki Sasanuma","orcid":"0000-0003-2824-4499","position":4,"is_corresponding":false},{"id":930825,"name":"Hisashi Tanaka","orcid":"0000-0001-9223-4186","position":5,"is_corresponding":false},{"id":49161,"name":"Yasuhiro Murakawa","orcid":"0000-0002-5415-1352","position":6,"is_corresponding":false},{"id":483349,"name":"Naoto Shimizu","orcid":"0000-0002-2046-9995","position":7,"is_corresponding":false},{"id":483348,"name":"Salma Akter","orcid":"0000-0002-2901-7784","position":8,"is_corresponding":false},{"id":757378,"name":"Masatoshi Takagi","orcid":"0000-0002-7580-9184","position":9,"is_corresponding":false},{"id":941560,"name":"Takuro Sunada","orcid":null,"position":10,"is_corresponding":false},{"id":941005,"name":"Shusuke Akamatsu","orcid":"0000-0002-1394-7506","position":11,"is_corresponding":false},{"id":941006,"name":"Gang He","orcid":"0000-0002-5319-7084","position":12,"is_corresponding":false},{"id":451623,"name":"Junji Itou","orcid":"0000-0002-0748-2327","position":13,"is_corresponding":false},{"id":701717,"name":"Masakazu Toi","orcid":"0000-0003-1488-9958","position":14,"is_corresponding":false},{"id":941007,"name":"Mary Miyaji","orcid":"0000-0003-3968-5994","position":15,"is_corresponding":false},{"id":941561,"name":"Kimiko Tsutsui","orcid":null,"position":16,"is_corresponding":false},{"id":254578,"name":"Scott Keeney","orcid":"0000-0002-1283-6417","position":17,"is_corresponding":false},{"id":266093,"name":"Shintaro Yamada","orcid":"0000-0002-4882-0871","position":18,"is_corresponding":false},{"id":941559,"name":"Rifat Ara Najnin","orcid":null,"position":0,"is_corresponding":true}],"reference_count":149,"raw_metadata":null,"created_at":"2026-07-19T00:28:03.504676Z","pmid":"36640339","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}