Linked Life Data

1587852

Source:http://linkedlifedata.com/resource/pubmed/id/1587852

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
1992-6-25
pubmed:abstractText
Specific metabolites of arachidonic and linoleic acid have been proposed as serving a regulatory function in growth factor signal transduction in fibroblasts. In studies with Syrian hamster embryo (SHE) fibroblasts, we found lipoxygenase inhibitors to be potent blockers of epidermal growth factor (EGF)-dependent mitogenesis. Analytical chemical characterization of arachidonic and linoleic acid metabolism in SHE cells demonstrated that the major lipoxygenase product was 13-hydroxyoctadecadienoic acid (HODE). EGF stimulation of quiescent SHE cells resulted in an enhancement of HODE biosynthesis. The primary arachidonate products were prostaglandin E2 and F2 alpha formed via the cyclooxygenase pathway. Inhibition of cyclooxygenase activity did not alter the EGF-mitogenic response in SHE cells. Addition of lipoxygenase-derived linoleate metabolites (10(-10)-10(-6) M) produced a 2-4-fold potentiation of EGF-stimulated [3H]thymidine incorporation in SHE cells. Interestingly, the linoleate products did not enhance the EGF mitogenic effect in variant SHE cells that had lost tumor suppressor gene function. These results were confirmed by autoradiographic studies of DNA synthesis and suggest that loss of tumor suppressor phenotype correlates with a lack of responsiveness to linoleate products in signal transduction. In studies on the mechanism of EGF regulation of linoleic acid metabolism, inhibitors of EGF receptor tyrosine kinase activity were observed to block EGF-stimulated HODE biosynthesis. In addition, both cyclohexamide and actinomycin D attenuated the ability of EGF to increase linoleic acid metabolism in SHE cells. EGF induction of the linoleate pathway appears to be linked to activation of the EGF receptor and may be modulated at transcriptional or translational levels.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
267
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10771-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:1587852-Animals, pubmed-meshheading:1587852-Arachidonic Acid, pubmed-meshheading:1587852-Autoradiography, pubmed-meshheading:1587852-Chromatography, High Pressure Liquid, pubmed-meshheading:1587852-Cricetinae, pubmed-meshheading:1587852-DNA, pubmed-meshheading:1587852-Dinoprost, pubmed-meshheading:1587852-Dinoprostone, pubmed-meshheading:1587852-Epidermal Growth Factor, pubmed-meshheading:1587852-Fibroblasts, pubmed-meshheading:1587852-Gas Chromatography-Mass Spectrometry, pubmed-meshheading:1587852-Genes, Tumor Suppressor, pubmed-meshheading:1587852-Linoleic Acid, pubmed-meshheading:1587852-Linoleic Acids, pubmed-meshheading:1587852-Lipoxygenase Inhibitors, pubmed-meshheading:1587852-Mesocricetus, pubmed-meshheading:1587852-Mitogens, pubmed-meshheading:1587852-Phenotype, pubmed-meshheading:1587852-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:1587852-Signal Transduction, pubmed-meshheading:1587852-Thymidine
pubmed:year
1992
pubmed:articleTitle
Modulation of the epidermal growth factor mitogenic response by metabolites of linoleic and arachidonic acid in Syrian hamster embryo fibroblasts. Differential effects in tumor suppressor gene (+) and (-) phenotypes.
pubmed:affiliation
Laboratoire of Molecular Biophysics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
pubmed:publicationType
Journal Article