Proteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer.
Background: Basal-like breast cancer (BLBC) is a poorly characterised, heterogeneous disease. Patients are diagnosed with aggressive, high-grade tumours and often relapse with chemotherapy resistance. Detailed understanding of the molecular underpinnings of this disease is essential to the developme...
| Publicado en: | Breast Cancer Research Vol. 22; no. 1; pp. 1 - 19 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
BioMed Central
6/11/2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=143724872&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 143724872 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14655411 8UYJ jtl: Breast Cancer Research issn: 14655411 maglogo: N pubinfo: dt: 6/11/2020 vid: 22 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 143724872 143724872 NLM32527287 143724872 10.1186/s13058-020-01306-6 NLM32527287 143724872 ppf: 1 ppct: 18 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Proteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer. aug: au: Baker, Laura A. Holliday, Holly Roden, Daniel Krisp, Christoph Wu, Sunny Z. Junankar, Simon Serandour, Aurelien A. Mohammed, Hisham Nair, Radhika Sankaranarayanan, Geetha Law, Andrew M. K. McFarland, Andrea Simpson, Peter T. Lakhani, Sunil Dodson, Eoin Selinger, Christina Anderson, Lyndal Samimi, Goli Hacker, Neville F. Lim, Elgene affil: The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, 2010, Darlinghurst, NSW, Australia sug: subj: Proteins Breast Neoplasms Carcinoma, Basal Cell Carcinoma, Basal Cell Metabolism Breast Neoplasms Metabolism Proteins Metabolism Cell Physiology Physiology Carcinoma, Basal Cell Pathology Human Breast Neoplasms Pathology Cell Differentiation Physiology Tumor Cells, Cultured Chromosomes Metabolism Prognosis Female Mice Cell Line, Tumor Apoptosis Physiology Animal Studies Xenografts DNA Chromosomes Validation Studies Comparative Studies Evaluation Research Multicenter Studies Coping Health Inventory for Parents Scales Female ab: Background: Basal-like breast cancer (BLBC) is a poorly characterised, heterogeneous disease. Patients are diagnosed with aggressive, high-grade tumours and often relapse with chemotherapy resistance. Detailed understanding of the molecular underpinnings of this disease is essential to the development of personalised therapeutic strategies. Inhibitor of differentiation 4 (ID4) is a helix-loop-helix transcriptional regulator required for mammary gland development. ID4 is overexpressed in a subset of BLBC patients, associating with a stem-like poor prognosis phenotype, and is necessary for the growth of cell line models of BLBC through unknown mechanisms.Methods: Here, we have defined unique molecular insights into the function of ID4 in BLBC and the related disease high-grade serous ovarian cancer (HGSOC), by combining RIME proteomic analysis, ChIP-seq mapping of genomic binding sites and RNA-seq.Results: These studies reveal novel interactions with DNA damage response proteins, in particular, mediator of DNA damage checkpoint protein 1 (MDC1). Through MDC1, ID4 interacts with other DNA repair proteins (γH2AX and BRCA1) at fragile chromatin sites. ID4 does not affect transcription at these sites, instead binding to chromatin following DNA damage. Analysis of clinical samples demonstrates that ID4 is amplified and overexpressed at a higher frequency in BRCA1-mutant BLBC compared with sporadic BLBC, providing genetic evidence for an interaction between ID4 and DNA damage repair deficiency.Conclusions: These data link the interactions of ID4 with MDC1 to DNA damage repair in the aetiology of BLBC and HGSOC. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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