Stimulation of DNA synthesis and cell proliferation of human mammary myoepithelial-like cells by hepatocyte growth factor/scatter factor depends on heparan sulfate proteoglycans and sustained phosphorylation of mitogen-activated protein kinases p42/44.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86361
Title:
Stimulation of DNA synthesis and cell proliferation of human mammary myoepithelial-like cells by hepatocyte growth factor/scatter factor depends on heparan sulfate proteoglycans and sustained phosphorylation of mitogen-activated protein kinases p42/44.
Authors:
Sergeant, Nicolas; Lyon, Malcolm; Rudland, Philip S; Fernig, David G; Delehedde, Maryse
Abstract:
Hepatocyte growth factor/scatter factor (HGF/SF) is a heparan/dermatan sulfate-binding growth factor produced by stromal cells that acts as a paracrine effector on neighboring epithelia. HGF/SF stimulated DNA synthesis in human mammary (Huma) 109 myoepithelial-like cells grown on collagen I and fibronectin substrata but not when grown on plastic. Dual phosphorylation of mitogen-activated protein kinases (p42/44(MAPK)) was required for this stimulation of DNA synthesis. In Huma 109 cells cultured on plastic, HGF/SF stimulated a transient phosphorylation of p42/44(MAPK), which reached a maximum at 10 min after addition of the growth factor and returned to near basal levels after 20 min. In contrast, the phosphorylation of p42/44(MAPK) stimulated by HGF/SF in cells cultured on collagen I or fibronectin was sustained over 45 min. In Huma 109 cells deficient in sulfated glycosaminoglycans, HGF/SF failed to stimulate p42/44(MAPK) phosphorylation or DNA synthesis on any substratum, even when soluble heparan sulfate proteoglycans purified from the cells or from the culture medium were added. However, HGF/SF stimulated DNA synthesis and a sustained phosphorylation of p42/44(MAPK) in sulfated glycosaminoglycan-deficient Huma 109 cells plated on a substratum of medium HSPGs but not cell HSPGs. The HGF/SF-induced proliferation is thus highly dependent on heparan sulfate proteoglycans in myoepithelial-like cells.
Affiliation:
School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, University of Manchester, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom.
Citation:
Stimulation of DNA synthesis and cell proliferation of human mammary myoepithelial-like cells by hepatocyte growth factor/scatter factor depends on heparan sulfate proteoglycans and sustained phosphorylation of mitogen-activated protein kinases p42/44. 2000, 275 (22):17094-9 J. Biol. Chem.
Journal:
The Journal of Biological Chemistry
Issue Date:
2-Jun-2000
URI:
http://hdl.handle.net/10541/86361
DOI:
10.1074/jbc.M000237200
PubMed ID:
10747885
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorSergeant, Nicolasen
dc.contributor.authorLyon, Malcolmen
dc.contributor.authorRudland, Philip Sen
dc.contributor.authorFernig, David Gen
dc.contributor.authorDelehedde, Maryseen
dc.date.accessioned2009-11-18T10:30:03Z-
dc.date.available2009-11-18T10:30:03Z-
dc.date.issued2000-06-02-
dc.identifier.citationStimulation of DNA synthesis and cell proliferation of human mammary myoepithelial-like cells by hepatocyte growth factor/scatter factor depends on heparan sulfate proteoglycans and sustained phosphorylation of mitogen-activated protein kinases p42/44. 2000, 275 (22):17094-9 J. Biol. Chem.en
dc.identifier.issn0021-9258-
dc.identifier.pmid10747885-
dc.identifier.doi10.1074/jbc.M000237200-
dc.identifier.urihttp://hdl.handle.net/10541/86361-
dc.description.abstractHepatocyte growth factor/scatter factor (HGF/SF) is a heparan/dermatan sulfate-binding growth factor produced by stromal cells that acts as a paracrine effector on neighboring epithelia. HGF/SF stimulated DNA synthesis in human mammary (Huma) 109 myoepithelial-like cells grown on collagen I and fibronectin substrata but not when grown on plastic. Dual phosphorylation of mitogen-activated protein kinases (p42/44(MAPK)) was required for this stimulation of DNA synthesis. In Huma 109 cells cultured on plastic, HGF/SF stimulated a transient phosphorylation of p42/44(MAPK), which reached a maximum at 10 min after addition of the growth factor and returned to near basal levels after 20 min. In contrast, the phosphorylation of p42/44(MAPK) stimulated by HGF/SF in cells cultured on collagen I or fibronectin was sustained over 45 min. In Huma 109 cells deficient in sulfated glycosaminoglycans, HGF/SF failed to stimulate p42/44(MAPK) phosphorylation or DNA synthesis on any substratum, even when soluble heparan sulfate proteoglycans purified from the cells or from the culture medium were added. However, HGF/SF stimulated DNA synthesis and a sustained phosphorylation of p42/44(MAPK) in sulfated glycosaminoglycan-deficient Huma 109 cells plated on a substratum of medium HSPGs but not cell HSPGs. The HGF/SF-induced proliferation is thus highly dependent on heparan sulfate proteoglycans in myoepithelial-like cells.en
dc.language.isoenen
dc.subject.meshBreast-
dc.subject.meshCell Division-
dc.subject.meshCells, Cultured-
dc.subject.meshCollagen-
dc.subject.meshDNA Replication-
dc.subject.meshFibronectins-
dc.subject.meshHeparan Sulfate Proteoglycans-
dc.subject.meshHepatocyte Growth Factor-
dc.subject.meshHumans-
dc.subject.meshMitogen-Activated Protein Kinases-
dc.subject.meshPhosphorylation-
dc.titleStimulation of DNA synthesis and cell proliferation of human mammary myoepithelial-like cells by hepatocyte growth factor/scatter factor depends on heparan sulfate proteoglycans and sustained phosphorylation of mitogen-activated protein kinases p42/44.en
dc.typeArticleen
dc.contributor.departmentSchool of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, University of Manchester, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom.en
dc.identifier.journalThe Journal of Biological Chemistryen

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