Genomic analysis of estrogen cascade reveals histone variant H2A.Z associated with breast cancer progression

Autor: Caleb B. Kallen, Olufunmilayo I. Olopade, David L. Rimm, Andrey Khramtsov, Maria Tretiakova, Christopher E. Mason, Parantu K. Shah, Sujun Hua, Jiang Liu, Kevin P. White, Ruby Dhar, Maria T Baquero, Thomas Krausz, Beth A Russell
Rok vydání: 2008
Předmět:
Breast Neoplasms
Biology
Models
Biological
Article
General Biochemistry
Genetics and Molecular Biology
Epigenesis
Genetic
Histones
Proto-Oncogene Proteins c-myc
03 medical and health sciences
0302 clinical medicine
Breast cancer
RNA interference
Biomarkers
Tumor
estrogen
medicine
Humans
cancer
Epigenetics
breast
030304 developmental biology
histone variant
0303 health sciences
Genome
Tiling array
Tissue microarray
General Immunology and Microbiology
Applied Mathematics
Estrogen Receptor alpha
Estrogens
medicine.disease
Chromatin
3. Good health
Gene expression profiling
Computational Theory and Mathematics
Lymphatic Metastasis
030220 oncology & carcinogenesis
Disease Progression
Cancer research
RNA Interference
General Agricultural and Biological Sciences
Chromatin immunoprecipitation
Information Systems
Zdroj: Molecular Systems Biology
ISSN: 1744-4292
DOI: 10.1038/msb.2008.25
Popis: 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.
Databáze: OpenAIRE
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