{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307693/"]},"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=GSE307693"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Transcriptomic profiling in estrogen-receptor positive cell line MCF7 following treatment with abemaciclib and fulvestrant","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":"2026/06/28"},"accession":"GSE307693","cross_references":{"GSM":["GSM9229439","GSM9229428","GSM9229427","GSM9229438","GSM9229429","GSM9229431","GSM9229442","GSM9229430","GSM9229441","GSM9229433","GSM9229444","GSM9229443","GSM9229432","GSM9229446","GSM9229435","GSM9229434","GSM9229445","GSM9229448","GSM9229426","GSM9229437","GSM9229436","GSM9229447","GSM9229425","GSM9229440"],"GPL":["18573"],"GSE":["307693"],"taxon":["Homo sapiens"]}}