PMID- 10747885 OWN - NLM STAT- MEDLINE DCOM- 20000711 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 275 IP - 22 DP - 2000 Jun 2 TI - 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. PG - 17094-9 AB - 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. FAU - Sergeant, N AU - Sergeant N AD - School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, University of Manchester, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom. FAU - Lyon, M AU - Lyon M FAU - Rudland, P S AU - Rudland PS FAU - Fernig, D G AU - Fernig DG FAU - Delehedde, M AU - Delehedde M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Fibronectins) RN - 0 (Heparan Sulfate Proteoglycans) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 9007-34-5 (Collagen) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Breast/*cytology MH - Cell Division/*physiology MH - Cells, Cultured MH - Collagen/metabolism MH - DNA Replication/*physiology MH - Fibronectins/metabolism MH - Heparan Sulfate Proteoglycans/*physiology MH - Hepatocyte Growth Factor/*physiology MH - Humans MH - Mitogen-Activated Protein Kinases/*metabolism MH - Phosphorylation EDAT- 2000/04/05 09:00 MHDA- 2000/07/15 11:00 CRDT- 2000/04/05 09:00 PHST- 2000/04/05 09:00 [pubmed] PHST- 2000/07/15 11:00 [medline] PHST- 2000/04/05 09:00 [entrez] AID - S0021-9258(19)80316-2 [pii] AID - 10.1074/jbc.M000237200 [doi] PST - ppublish SO - J Biol Chem. 2000 Jun 2;275(22):17094-9. doi: 10.1074/jbc.M000237200.