Linked Life Data

17932744

Source:http://linkedlifedata.com/resource/pubmed/id/17932744

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-7-16
pubmed:abstractText
Estrogen receptor alpha (ER) and its ligand estrogen play vital roles in the development, progression and treatment of breast cancer. An increasing number of studies have also provided evidence linking disruption of the Fanconi anemia/BRCA cascade to breast cancer. Our objectives were to examine the methylation status and expression profiles of ER, correlate the findings with BRCA1 and FANCF methylation and map the critical CpGs for ER expression. We found that the CpG islands in the 5' region of the ER gene are methylated in 59 of 120 (49.2%) primary breast cancers, including 45 of 59 ER-negative tumors (76.3%, P < 0.00001). In addition, we observed a strong correlation between ER promoter and BRCA1 promoter methylation (odds ratio 3.12, 95% confidence interval 1.10-9.68, P = 0.02). In contrast, FANCF methylation was rare in breast tumors: one of 120 (0.8%). ER methylation was associated with high tumor grade (60.4% methylated vs. 39.6% unmethylated in grade 3 tumors, P = 0.04) and tumor subtype (P = 0.03). Though small in number, all tumors of the medullary subtype were ER methylated. In contrast, the lobular subtype had the least methylation (23.1% methylated vs. 76.9% unmethylated). After treatment of MDA-MB-231 cells with 5-aza-cytidine (5-aza-dC) and trichostatin, which resulted in re-expression of ER mRNA, we localized dramatic demethylation effects to CpG islands in positions +68, +165, +192, +195, +337, +341 and +405 from transcription start site of the ER promoter. These data suggest that unlike FANCF, both ER and BRCA1 are specifically targeted for methylation in sporadic breast cancers, a phenomenon that should be explored for development of novel diagnostic and therapeutic approaches.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0167-6806
pubmed:author
pubmed:issnType
Print
pubmed:volume
111
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
113-20
pubmed:dateRevised
2009-10-22
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Estrogen receptor alpha, BRCA1, and FANCF promoter methylation occur in distinct subsets of sporadic breast cancers.
pubmed:affiliation
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637-1463, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural