{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336731/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336731"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Transcriptomic profiling of MCF7 ESR1-PARENT and ESR1-Y537S cells cultured under estrogen-depleted or estradiol-supplemented conditions following abemaciclib treatment and CCND1 knockdown","description":"The retinoblastoma protein (Rb) is a tumour suppressor best known for repressing E2F transcription factors and halting cell cycle progression. In hormone receptor-positive (HR+) breast cancer, CDK4/6 inhibitors activate Rb by preventing its phosphorylation, forming a key component of current endocrine therapy regimens. How pharmacologically activated Rb remodels chromatin and influences transcription beyond cell cycle arrest remains poorly understood. Here we show that CDK4/6 inhibition induces redistribution of hypo-phosphorylated Rb to promoters and enhancers. While Rb predictably binds to cell cycle gene promoters to repress transcription, at other sites it unexpectedly promotes expression of oestrogen-responsive genes by integrating into oestrogen receptor (ER)-rich transcriptional hubs. CDK4/6 inhibition enhances ER target gene expression in breast cancer cells, patient-derived xenografts, and clinical HR+ breast cancer samples in an Rb-dependent manner. This reprogramming is mediated in part by KDM5A, whose interaction with Rb contributes to gene regulation at these loci. Critically, components of this Rb-driven ER transcriptional program are pro-proliferative. In endocrine-sensitive tumours, this can be neutralised with anti-oestrogen therapy, explaining therapeutic synergy. In endocrine-resistant settings such as ESR1-mutant breast cancer, the program persists, limiting therapeutic efficacy. These findings reframe Rb as a dual-function transcriptional regulator that, while enforcing cell cycle arrest, can also activate programs that counteract its tumour suppressor function.","dates":{"publication":"2026/06/29"},"accession":"GSE336731","cross_references":{"GSM":["GSM9841480","GSM9841503","GSM9841469","GSM9841502","GSM9841501","GSM9841468","GSM9841489","GSM9841500","GSM9841488","GSM9841487","GSM9841486","GSM9841485","GSM9841484","GSM9841483","GSM9841482","GSM9841481","GSM9841491","GSM9841490","GSM9841479","GSM9841478","GSM9841477","GSM9841499","GSM9841498","GSM9841476","GSM9841497","GSM9841475","GSM9841496","GSM9841474","GSM9841495","GSM9841473","GSM9841472","GSM9841494","GSM9841493","GSM9841471","GSM9841492","GSM9841470"],"GPL":["18573"],"GSE":["336731"],"taxon":["Homo sapiens"]}}