Open AccessGenomic analysis of estrogen cascade reveals histone variant H2A.Z associated with breast cancer progression
Author(s) -
Hua Sujun,
Kallen Caleb B,
Dhar Ruby,
Baquero Maria T,
Mason Christopher E,
Russell Beth A,
Shah Parantu K,
Liu Jiang,
Khramtsov Andrey,
Tretiakova Maria S,
Krausz Thomas N,
Olopade Olufunmilayo I,
Rimm David L,
White Kevin P
Publication year - 2008
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2008.25
Subject(s) - biology , epigenetics , chromatin immunoprecipitation , breast cancer , histone , cancer research , gene expression profiling , chromatin , regulation of gene expression , gene , cancer , gene expression , genetics , promoter
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 ERα 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.