Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-6-22
pubmed:abstractText
Primates and equids are the only species known to express the placental glycoprotein hormone, chorionic gonadotropin (CG), a heterodimeric glycoprotein composed of an alpha subunit linked to a hormone-specific beta subunit. The regulatory mechanisms involved in the induction of equine glycoprotein alpha subunit gene expression have not been identified. Epidermal growth factor (EGF) receptor is known to transduce signals that alter a number of different cellular functions (cell proliferation, differentiation, hormone secretion, and gene regulation). In the present study, we investigated the regulation of the equine alpha subunit gene by EGF in trophoblasts. We found that 2800 base pairs of 5' flanking sequence from the equine alpha subunit promoter is sufficient for basal expression in human choriocarcinoma cells. Epidermal growth factor and phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), increased transcriptional activity of the equine alpha subunit promoter (-2800/+21). These responses were blocked by pretreatment with bisindolylmaleimide-I, an inhibitor of PKC, suggesting an involvement of this pathway downstream of EGF. In addition, PD98059, an inhibitor of the extracellular signal-regulated kinase (ERK) pathway, completely blocked activation of the equine alpha promoter by PMA, suggesting that mitogen-activated protein kinase (MAPK) cascade was involved downstream of the PKC pathway. In conclusion, the EGF/PKC/MAPK pathway regulates equine glycoprotein alpha subunit gene expression through a distinct regulatory region (-2300 to -1900) in trophoblasts, while essential elements for basal expression appear to exist within the -2800 to -1900 region of the promoter.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-3363
pubmed:author
pubmed:issnType
Print
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
197-203
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11420240-Animals, pubmed-meshheading:11420240-Cells, Cultured, pubmed-meshheading:11420240-Enzyme Activators, pubmed-meshheading:11420240-Enzyme Inhibitors, pubmed-meshheading:11420240-Epidermal Growth Factor, pubmed-meshheading:11420240-Female, pubmed-meshheading:11420240-Flavonoids, pubmed-meshheading:11420240-Glycoprotein Hormones, alpha Subunit, pubmed-meshheading:11420240-Horses, pubmed-meshheading:11420240-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:11420240-Plasmids, pubmed-meshheading:11420240-Promoter Regions, Genetic, pubmed-meshheading:11420240-Protein Kinase C, pubmed-meshheading:11420240-Signal Transduction, pubmed-meshheading:11420240-Tetradecanoylphorbol Acetate, pubmed-meshheading:11420240-Transfection, pubmed-meshheading:11420240-Trophoblasts
pubmed:year
2001
pubmed:articleTitle
Epidermal growth factor regulation of equine glycoprotein hormone alpha subunit expression in trophoblast cells.
pubmed:affiliation
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160-7401, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't