Linked Life Data

16109739

Source:http://linkedlifedata.com/resource/pubmed/id/16109739

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-12-28
pubmed:abstractText
The progesterone receptor (PR) plays roles in normal mammary development and breast cancer formation, where it may exert both stimulatory and inhibitory actions. Previously, the breast cancer susceptibility gene product BRCA1 was found to interact with and inhibit the transcriptional activity of estrogen receptor-alpha. In this study, we found that exogenous wild-type BRCA1 inhibited the activity of the PR in transient transfection assays utilizing a mouse mammary tumor virus-Luc reporter. Wild-type BRCA1 inhibited the activity of endogenous PR in human breast cancer cells (T47D and MCF-7) and inhibited the activity of exogenous PR-A, PR-B, and [PR-A plus PR-B] isoforms. On the other hand, knockdown of endogenous BRCA1 using small interfering RNA enhanced the progesterone-stimulated activity of the PR by about 4-fold. We documented an in vivo association of the endogenous BRCA1 with PR isoforms A and B and a direct in vitro interaction between BRCA1 and PR, which was partially mapped. Whereas down-regulation of the coactivator p300 contributes to the BRCA1-mediated repression of estrogen receptor-alpha, this mechanism does not contribute to inhibition of PR activity, because exogenous p300 did not rescue the BRCA1 repression of PR activity. The BRCA1-PR interaction has functional consequences. Thus, we showed that BRCA1 inhibits the expression of various endogenous progesterone-responsive genes and inhibits progesterone-stimulated proliferation of T47D cells. Finally, exogenous progesterone caused an exaggerated proliferative response in the mammary glands of mice harboring a mammary-targeted conditional deletion of the full-length isoform of Brca1. These findings suggest that BRCA1 regulates the activity of progesterone, a major hormone of pregnancy that may also participate in mammary carcinogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14-34
pubmed:dateRevised
2011-1-24
pubmed:meshHeading
pubmed-meshheading:16109739-Animals, pubmed-meshheading:16109739-BRCA1 Protein, pubmed-meshheading:16109739-Cell Line, Tumor, pubmed-meshheading:16109739-Cell Proliferation, pubmed-meshheading:16109739-Epithelial Cells, pubmed-meshheading:16109739-Estrogen Receptor alpha, pubmed-meshheading:16109739-Gene Expression Regulation, pubmed-meshheading:16109739-Humans, pubmed-meshheading:16109739-Mammary Glands, Animal, pubmed-meshheading:16109739-Mammary Tumor Virus, Mouse, pubmed-meshheading:16109739-Mice, pubmed-meshheading:16109739-Mice, Knockout, pubmed-meshheading:16109739-Mutation, pubmed-meshheading:16109739-Progesterone, pubmed-meshheading:16109739-Promoter Regions, Genetic, pubmed-meshheading:16109739-Protein Binding, pubmed-meshheading:16109739-Protein Isoforms, pubmed-meshheading:16109739-RNA, Small Interfering, pubmed-meshheading:16109739-Receptors, Progesterone, pubmed-meshheading:16109739-Signal Transduction, pubmed-meshheading:16109739-p300-CBP Transcription Factors
pubmed:year
2006
pubmed:articleTitle
The breast cancer susceptibility gene BRCA1 regulates progesterone receptor signaling in mammary epithelial cells.
pubmed:affiliation
Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC 20057-1469, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural