Linked Life Data

10517668

Source:http://linkedlifedata.com/resource/pubmed/id/10517668

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1999-12-22
pubmed:abstractText
The human progesterone receptor (PR) is expressed as two isoforms, PRA and PRB, which differ in the N-terminal region and exhibit different activities in vitro, with PRA demonstrating dominant negative inhibitory effects on the activity of PRB and other nuclear receptors. PRA and PRB are expressed in target tissues at comparable levels although cells expressing a predominance of one isoform can be identified. In breast cancers, PRA is expressed at high levels in some tumors, and this may be associated with features of poorer prognosis. To investigate the role of PRA overexpression in PR-positive target cells, the effect of PRA induction on cell proliferation and expression of endogenous progestin-sensitive genes, SOX4 and fatty acid synthetase (FAS), was examined using PR-positive T-47D cell lines, which express a predominance of PRB, in which PRA could be increased 2- to 20-fold over basal levels. No effect of PRA induction was noted on cell proliferation, but marked changes in morphology, consistent with loss of adherent properties, were observed. Increases up to 4-fold in the relative PRA levels augmented progestin induction of SOX4 mRNA expression, and RU486 treatment revealed a progestin agonist effect. There was no consistent effect of PRA induction on progestin-mediated increases in FAS mRNA levels under these conditions. Clones with PRA:PRB ratios greater than 15 were associated with diminished progestin responses on both SOX4 and FAS mRNA expression. These data show that PRA overexpression is associated with alteration in adhesive properties in breast cancer cells and effects on endogenous progestin targets that were dependent on the cellular ratio of PRA:PRB. The results of this study are consistent with the view that PRA expression can fluctuate within a broad range in target cells without influencing the nature of progestin action on downstream targets, but that overexpression of PRA, such as is seen in a proportion of breast cancers, may be associated with inhibition of progestin action and features of poor prognosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1657-71
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10517668-Breast Neoplasms, pubmed-meshheading:10517668-Cell Division, pubmed-meshheading:10517668-Fatty Acid Synthetase Complex, pubmed-meshheading:10517668-Female, pubmed-meshheading:10517668-Gene Expression Regulation, Neoplastic, pubmed-meshheading:10517668-High Mobility Group Proteins, pubmed-meshheading:10517668-Humans, pubmed-meshheading:10517668-Isopropyl Thiogalactoside, pubmed-meshheading:10517668-Plasmids, pubmed-meshheading:10517668-Progestins, pubmed-meshheading:10517668-Receptors, Progesterone, pubmed-meshheading:10517668-SOXC Transcription Factors, pubmed-meshheading:10517668-Time Factors, pubmed-meshheading:10517668-Trans-Activators, pubmed-meshheading:10517668-Transcription, Genetic, pubmed-meshheading:10517668-Transfection, pubmed-meshheading:10517668-Tumor Cells, Cultured
pubmed:year
1999
pubmed:articleTitle
Effect of overexpression of progesterone receptor A on endogenous progestin-sensitive endpoints in breast cancer cells.
pubmed:affiliation
Westmead Institute for Cancer Research, University of Sydney, Westmead Hospital, New South Wales, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't