Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2011-6-13
pubmed:abstractText
In postmenopausal breast cancers, the increase in aromatase expression observed in tumour associated adipose stromal cells is mediated via the upregulation of promoter II (PII) transcription. Factors such as PGE? which are secreted from breast carcinomas induce PII expression. The orphan nuclear receptor LRH-1/NR5A2 is one of the critical downstream transcriptional mediators of this effect. The aim of the current study was to determine whether LRH-1 could bind directly to PII and whether the suppression of LRH-1 expression could inhibit aromatase expression in human adipose stromal fibroblasts. Chromatin immunoprecipitation demonstrated endogenous LRH-1 occupancy on PII under basal conditions and with treatment with forskolin and phorbol 12-myristate 13-acetate (PMA). To assess the impact of LRH-1 knockdown on FSK/PMA mediated PII expression, cells were transfected with shRNA targeted against LRH-1 (shLRH-1) and treated with forskolin and PMA. A decrease in LRH-1, PII and total aromatase mRNA transcripts was observed in shLRH-1 transfected cells compared to controls under basal and treatment conditions. The results of this study support the hypothesis that suppression of LRH-1 may potentially be beneficial in the tissue specific regulation of aromatase expression in post menopausal breast cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1878-5867
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
76
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
741-4
pubmed:meshHeading
pubmed-meshheading:21392518-Adipose Tissue, pubmed-meshheading:21392518-Aromatase, pubmed-meshheading:21392518-Breast, pubmed-meshheading:21392518-Breast Neoplasms, pubmed-meshheading:21392518-Chromatin Immunoprecipitation, pubmed-meshheading:21392518-Dinoprostone, pubmed-meshheading:21392518-Female, pubmed-meshheading:21392518-Fibroblasts, pubmed-meshheading:21392518-Forskolin, pubmed-meshheading:21392518-Gene Expression Regulation, Enzymologic, pubmed-meshheading:21392518-Gene Expression Regulation, Neoplastic, pubmed-meshheading:21392518-Gene Knockout Techniques, pubmed-meshheading:21392518-Humans, pubmed-meshheading:21392518-Organ Specificity, pubmed-meshheading:21392518-Postmenopause, pubmed-meshheading:21392518-Promoter Regions, Genetic, pubmed-meshheading:21392518-RNA, Small Interfering, pubmed-meshheading:21392518-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:21392518-Stromal Cells, pubmed-meshheading:21392518-Tetradecanoylphorbol Acetate, pubmed-meshheading:21392518-Transfection
pubmed:year
2011
pubmed:articleTitle
Tissue-specific regulation of aromatase promoter II by the orphan nuclear receptor LRH-1 in breast adipose stromal fibroblasts.
pubmed:affiliation
Prince Henry's Institute, Monash Medical Centre, 246 Clayton Road, Clayton, Melbourne, Vic 3168, Australia. ashwini.chand@princehenrys.org
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't