Linked Life Data

11016753

Source:http://linkedlifedata.com/resource/pubmed/id/11016753

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-1-3
pubmed:abstractText
Approximately two thirds of breast cancer patients have estrogen-dependent carcinomas. The biosynthesis of estrogens is catalyzed by the microsomal enzyme aromatase. Mechanisms controlling human aromatase gene expression are complicated by the existence of multiple tissue specific promoters. The most proximally located Pll promoter is mainly active in ovarian granulosa cells. PlI can be switched on in human breast cancer cells. Since there are strong silencer elements located within the 3' portion of the PlI promoter, we propose that the function of these silencer elements could be reversed by breast cancer cell specific signals/factors, resulting in aberrant expression of aromatase. We have identified and characterized a novel silencer element, S2, which is upstream of S1, a silencer element recently identified by another group. S2, a 54-bp fragment 100% conserved between humans and rodents, functions in both orientation- and promoter-independent manners. The core region of S2 contains two consensus binding sites for members of the GATA transcription factors. GATA-4 was found to be expressed in three out of four human breast cancer cell lines examined by RT-PCR, and transfection with GATA-4 partially reversed the repressive function of S2. However, we were unable to demonstrate that DNA-protein complexes formed between nuclear extracts of human breast and ovarian cancer cells and S2 contain GATA-4 using a supershifting approach. We suggest that the expression of GATA-4, and more importantly, other yet to be identified GATA or GATA-related factor(s), are implicated in provoking aberrant expression of aromatase, and therefore, the biosynthesis of estrogens, in human breast cancer cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0167-6806
pubmed:author
pubmed:issnType
Print
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
151-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Characterization of a novel silencer element in the human aromatase gene PII promoter.
pubmed:affiliation
Division of Cell and Molecular Biology, Toronto General Research Institute, University of Toronto, Ontario, Canada. tianru.jin@utoronto.ca
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't