PMID- 15140946
OWN - NLM
STAT- MEDLINE
DCOM- 20050218
LR  - 20211203
IS  - 1541-7786 (Print)
IS  - 1541-7786 (Linking)
VI  - 2
IP  - 4
DP  - 2004 Apr
TI  - Multiple aspects of the phenotype of mammary epithelial cells transformed by 
      expression of activated M-Ras depend on an autocrine mechanism mediated by 
      hepatocyte growth factor/scatter factor.
PG  - 242-55
AB  - Multiple aspects of the transformed phenotype induced in a murine mammary 
      epithelial cell line scp-2 by expression of activated G22V M-Ras, including 
      maintainance of cell number at low density, anchorage-independent growth, 
      invasion of Matrigel, and secretion of matrix metalloproteinases (MMP) 2 and 9, 
      were dependent on an autocrine mechanism. Conditioned medium from dense cultures 
      of scp-2 cells expressing G22V M-Ras, but not from parental cells, induced 
      activation of Erk and Akt in cells expressing G22V M-Ras, maintained the cell 
      number and promoted anchorage-independent growth of cells expressing G22V M-Ras 
      (although not the parental cells), and induced scattering of MDCK cells. The 
      latter activities were blocked by neutralizing antibodies to hepatocyte growth 
      factor/scatter factor (HGF/SF) and could be mimicked by HGF/SF. Anti-HGF/SF 
      antibodies also inhibited invasion of Matrigel, and the production of MMP-2 and 
      MMP-9, together with urokinase-type plasminogen activator, was secreted by G22V 
      M-Ras scp-2 cells but not by parental cells. Invasion of Matrigel was blocked by 
      an inhibitor of MMPs, BB94, and by the mitogen-activated protein kinase kinase 
      1/2 kinase inhibitor PD98059 but was only marginally affected by the 
      phosphatidylinositol 3-kinase inhibitor LY294002. Autocrine HGF/SF was thus 
      critical for expression of key features of the phenotype of mammary epithelial 
      cells transformed by expression of activated M-Ras.
FAU - Zhang, Kai-Xin
AU  - Zhang KX
AD  - The Biomedical Research Centre, University of British Columbia, Vancouver, 
      British Columbia, Canada.
FAU - Ward, Katherine R
AU  - Ward KR
FAU - Schrader, John W
AU  - Schrader JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cancer Res
JT  - Molecular cancer research : MCR
JID - 101150042
RN  - 0 (Antibodies)
RN  - 0 (Blood Proteins)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.6.1.- (Mras protein, mouse)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Autocrine Communication/*drug effects
MH  - Blood Proteins/pharmacology
MH  - Cell Count
MH  - Cell Division/drug effects/physiology
MH  - Cell Line
MH  - Cell Transformation, Neoplastic/*chemically induced/genetics/*pathology
MH  - Contact Inhibition
MH  - Culture Media, Conditioned/pharmacology
MH  - Culture Media, Serum-Free/pharmacology
MH  - Enzyme Activation/drug effects
MH  - Epithelial Cells/metabolism/*pathology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Gene Expression
MH  - Hepatocyte Growth Factor/*pharmacology
MH  - Mammary Glands, Animal/*pathology
MH  - Mice
MH  - Monomeric GTP-Binding Proteins/genetics/*metabolism
MH  - Mutation
MH  - Neoplasm Invasiveness
MH  - Phenotype
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - ras Proteins
EDAT- 2004/05/14 05:00
MHDA- 2005/02/19 09:00
CRDT- 2004/05/14 05:00
PHST- 2004/05/14 05:00 [pubmed]
PHST- 2005/02/19 09:00 [medline]
PHST- 2004/05/14 05:00 [entrez]
PST - ppublish
SO  - Mol Cancer Res. 2004 Apr;2(4):242-55.