title: Genomic analysis of estrogen cascade reveals histone variant H2A.Z associated with breast cancer progression.
abstract: We demonstrate an integrated approach to the study of a transcriptional regulatory cascade involved in the progression of breast cancer and we identify a protein associated with disease progression. Using chromatin immunoprecipitation and genome tiling arrays, whole genome mapping of transcription factor-binding sites was combined with gene expression profiling to identify genes involved in the proliferative response to estrogen (E2). Using RNA interference, selected ERalpha and c-MYC gene targets were knocked down to identify mediators of E2-stimulated cell proliferation. Tissue microarray screening revealed that high expression of an epigenetic factor, the E2-inducible histone variant H2A.Z, is significantly associated with lymph node metastasis and decreased breast cancer survival. Detection of H2A.Z levels independently increased the prognostic power of biomarkers currently in clinical use. This integrated approach has accelerated the identification of a molecule linked to breast cancer progression, has implications for diagnostic and therapeutic interventions, and can be applied to a wide range of cancers.
authors.affiliation: Joint Institute for Genomics and Systems Biology, The University of Chicago and Argonne National Laboratory, Chicago, IL, USA.
authors.forename: Sujun
authors.initials: S
authors.lastname: Hua
authors.forename: Caleb B
authors.initials: CB
authors.lastname: Kallen
authors.forename: Ruby
authors.initials: R
authors.lastname: Dhar
authors.forename: Maria T
authors.initials: MT
authors.lastname: Baquero
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Mason
authors.forename: Beth A
authors.initials: BA
authors.lastname: Russell
authors.forename: Parantu K
authors.initials: PK
authors.lastname: Shah
authors.forename: Jiang
authors.initials: J
authors.lastname: Liu
authors.forename: Andrey
authors.initials: A
authors.lastname: Khramtsov
authors.forename: Maria S
authors.initials: MS
authors.lastname: Tretiakova
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Krausz
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: David L
authors.initials: DL
authors.lastname: Rimm
authors.forename: Kevin P
authors.initials: KP
authors.lastname: White
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D002843:Chromatin / Q000737:chemistry; D018450:Disease Progression; D044127:Epigenesis, Genetic; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D016678:Genome; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008207:Lymphatic Metastasis; D008954:Models, Biological; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034622:RNA Interference
chemical_list: D014408:Biomarkers, Tumor; D002843:Chromatin; D047628:Estrogen Receptor alpha; D004967:Estrogens; D006657:Histones; D016271:Proto-Oncogene Proteins c-myc