{"doi":"10.1111/acel.13665","title":"Age alters the oncogenic trajectory toward luminal mammary tumors that activate unfolded proteins responses","abstract":"A major limitation in the use of mouse models in breast cancer research is that most mice develop estrogen receptor-alpha (ERα)-negative mammary tumors, while in humans, the majority of breast cancers are ERα-positive. Therefore, developing mouse models that best mimic the disease in humans is of fundamental need. Here, using an inducible MMTV-rtTA/TetO-NeuNT mouse model, we show that despite being driven by the same oncogene, mammary tumors in young mice are ERα-negative, while they are ERα-positive in aged mice. To further elucidate the mechanisms for this observation, we performed RNAseq analysis and identified genes that are uniquely expressed in aged female-derived mammary tumors. We found these genes to be involved in the activation of the ERα axis of the mitochondrial UPR and the ERα-mediated regulation of XBP-1s, a gene involved in the endoplasmic reticulum UPR. Collectively, our results indicate that aging alters the oncogenic trajectory towards the ERα-positive subtype of breast cancers, and that mammary tumors in aged mice are characterized by the upregulation of multiple UPR stress responses regulated by the ERα.","journal":"Aging Cell","year":2022,"id":267727,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"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":728101,"name":"Mrittika Chattopadhyay","orcid":null,"position":1,"is_corresponding":false},{"id":459079,"name":"Maria Gomez-Jenkins","orcid":"0000-0003-3682-9219","position":2,"is_corresponding":false},{"id":74685,"name":"Denis Torre","orcid":"0000-0003-4615-223X","position":3,"is_corresponding":false},{"id":60353,"name":"Avi Ma’ayan","orcid":"0000-0002-6904-1017","position":4,"is_corresponding":false},{"id":621646,"name":"Miguel Torres‐Martín","orcid":"0000-0003-1589-8936","position":5,"is_corresponding":false},{"id":231499,"name":"Daniela Sia","orcid":"0000-0002-9000-611X","position":6,"is_corresponding":false},{"id":459081,"name":"Doris Germain","orcid":"0000-0001-6597-0196","position":7,"is_corresponding":false},{"id":459078,"name":"Edmund C. Jenkins","orcid":"0000-0002-6448-090X","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T00:27:06.198948Z","pmid":"36111352","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":[]}