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Genomic analysis of estrogen cascade reveals histone variant H2A.Z associated with breast cancer progression.
- Source :
-
Molecular systems biology [Mol Syst Biol] 2008; Vol. 4, pp. 188. Date of Electronic Publication: 2008 Apr 15. - Publication Year :
- 2008
-
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.
- Subjects :
- Biomarkers, Tumor metabolism
Chromatin chemistry
Disease Progression
Epigenesis, Genetic
Estrogen Receptor alpha metabolism
Genome
Humans
Lymphatic Metastasis
Models, Biological
Proto-Oncogene Proteins c-myc metabolism
RNA Interference
Breast Neoplasms metabolism
Estrogens metabolism
Histones chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1744-4292
- Volume :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular systems biology
- Publication Type :
- Academic Journal
- Accession number :
- 18414489
- Full Text :
- https://doi.org/10.1038/msb.2008.25