Linked Life Data

10595400

Source:http://linkedlifedata.com/resource/pubmed/id/10595400

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2000-1-4
pubmed:abstractText
The prototypic member of the transforming growth factor beta family is TGFbeta1, which is known to be important in extracellular matrix production, cell proliferation, and cell differentiation. Specifically in the pituitary lactotroph, TGFbeta1 inhibits prolactin (PRL) peptide secretion, PRL mRNA levels, and PRL gene transcription. To further elucidate the molecular details by which TGFbeta1 modulates PRL gene transcription, we used a transient transfection approach to characterize and to map the TGFbeta1 inhibitory response element of the rat (r) PRL promoter. Here, we show that TGFbeta1 selectively inhibits basal rPRL promoter activity in GH4 cells in a dose-responsive fashion, with an IC50 of 6 pM, and that this inhibition occurs within 6 h after TGFbeta1 addition. Using a series of 5' deletion promoter mutants, the TGFbeta1 inhibitory response was found to be unaffected by deletion to position -116 and was abrogated by further deletion to -54 in the rPRL promoter. However, on the basis of data from site-specific and linker-scanning mutants of the rPRL promoter, it appears that no single element is sufficient to mediate the TGFbeta1 inhibitory effect. Sequence analysis of the -116/-54 region failed to reveal any sequence homology to previously characterized TGFbeta response elements. Finally, TGFbeta1 failed to alter significantly the endogenous levels of the cell-specific activator protein GHF-1/Pit-1, indicating that the TGFbeta1 inhibitory effect is not attributable to diminished levels of GHF-1/Pit-1. Taken together, these data indicate that the TGFbeta1 inhibitory response is more complex than previously appreciated, requiring more than one cis-acting element and not always acting via TTGG or GTCTAGAC sites.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1044-5498
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
863-73
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10595400-Animals, pubmed-meshheading:10595400-Base Sequence, pubmed-meshheading:10595400-Blotting, Western, pubmed-meshheading:10595400-Cell Line, pubmed-meshheading:10595400-DNA-Binding Proteins, pubmed-meshheading:10595400-Gene Expression Regulation, pubmed-meshheading:10595400-Genes, Reporter, pubmed-meshheading:10595400-Humans, pubmed-meshheading:10595400-Luciferases, pubmed-meshheading:10595400-Molecular Sequence Data, pubmed-meshheading:10595400-Pituitary Gland, pubmed-meshheading:10595400-Prolactin, pubmed-meshheading:10595400-Promoter Regions, Genetic, pubmed-meshheading:10595400-Rats, pubmed-meshheading:10595400-Sequence Deletion, pubmed-meshheading:10595400-Transcription Factor Pit-1, pubmed-meshheading:10595400-Transcription Factors, pubmed-meshheading:10595400-Transfection, pubmed-meshheading:10595400-Transforming Growth Factor beta
pubmed:year
1999
pubmed:articleTitle
Transforming growth factor-beta1 inhibits rat prolactin promoter activity in GH4 neuroendocrine cells.
pubmed:affiliation
Department of Medicine, Program in Molecular Biology, Colorado Cancer Center, University of Colorado Health Sciences Center, Denver 80262, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.