Transfer of motogenic and invasive response to scatter factor/hepatocyte growth factor by transfection of human MET protooncogene

S. Giordano, Z. Zhen, E. Medico, G. Gaudino, F. Galimi, P. M. Comoglio

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

The MET protooncogene encodes p190MET, a tyrosine kinase which is the receptor for a molecule known as scatter factor or hepatocyte growth factor (SF/HGF). This molecule has different biological activities, including stimulation of cell motility, promotion of matrix invasion and, in some cells, mitogenesis. We have cloned the full-length MET cDNA and transfected it into NIH 3T3 fibroblasts. Stable transfectants expressed the p190MET receptor together with two previously described truncated forms of 140 and 130 kDa lacking the tyrosine kinase domain. All three forms bound radiolabeled SF/HGF. The factor stimulated tyrosine kinase activity of the transfected p190MET and induced changes in cell shape, migration in Boyden chambers, and invasion of collagen matrices in vitro. The motile and invasive phenotype was transient and strictly dependent on the presence of SF/HGF. The factor did not stimulate either cell growth or thymidine incorporation in transfected cells, while it promoted colony formation in soft agar in the presence of 5% fetal calf serum. These data show that, in the presence of its ligand, the MET receptor expressed in fibroblasts induces cells to pursue a motogenic-invasive rather than a proliferative program.

Original languageEnglish
Pages (from-to)649-653
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number2
Publication statusPublished - Jan 15 1993

Fingerprint

Hepatocyte Growth Factor
Transfection
Protein-Tyrosine Kinases
Cell Movement
Fibroblasts
Cell Shape
Thymidine
Agar
human HGF protein
Collagen
Complementary DNA
Ligands
Phenotype
Growth
Serum

Keywords

  • Invasion
  • Tyrosine kinase receptors

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

@article{eb874a28f7e349beb37739e3b8e607f9,
title = "Transfer of motogenic and invasive response to scatter factor/hepatocyte growth factor by transfection of human MET protooncogene",
abstract = "The MET protooncogene encodes p190MET, a tyrosine kinase which is the receptor for a molecule known as scatter factor or hepatocyte growth factor (SF/HGF). This molecule has different biological activities, including stimulation of cell motility, promotion of matrix invasion and, in some cells, mitogenesis. We have cloned the full-length MET cDNA and transfected it into NIH 3T3 fibroblasts. Stable transfectants expressed the p190MET receptor together with two previously described truncated forms of 140 and 130 kDa lacking the tyrosine kinase domain. All three forms bound radiolabeled SF/HGF. The factor stimulated tyrosine kinase activity of the transfected p190MET and induced changes in cell shape, migration in Boyden chambers, and invasion of collagen matrices in vitro. The motile and invasive phenotype was transient and strictly dependent on the presence of SF/HGF. The factor did not stimulate either cell growth or thymidine incorporation in transfected cells, while it promoted colony formation in soft agar in the presence of 5{\%} fetal calf serum. These data show that, in the presence of its ligand, the MET receptor expressed in fibroblasts induces cells to pursue a motogenic-invasive rather than a proliferative program.",
keywords = "Invasion, Tyrosine kinase receptors",
author = "S. Giordano and Z. Zhen and E. Medico and G. Gaudino and F. Galimi and Comoglio, {P. M.}",
year = "1993",
month = "1",
day = "15",
language = "English",
volume = "90",
pages = "649--653",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "2",

}

TY - JOUR

T1 - Transfer of motogenic and invasive response to scatter factor/hepatocyte growth factor by transfection of human MET protooncogene

AU - Giordano, S.

AU - Zhen, Z.

AU - Medico, E.

AU - Gaudino, G.

AU - Galimi, F.

AU - Comoglio, P. M.

PY - 1993/1/15

Y1 - 1993/1/15

N2 - The MET protooncogene encodes p190MET, a tyrosine kinase which is the receptor for a molecule known as scatter factor or hepatocyte growth factor (SF/HGF). This molecule has different biological activities, including stimulation of cell motility, promotion of matrix invasion and, in some cells, mitogenesis. We have cloned the full-length MET cDNA and transfected it into NIH 3T3 fibroblasts. Stable transfectants expressed the p190MET receptor together with two previously described truncated forms of 140 and 130 kDa lacking the tyrosine kinase domain. All three forms bound radiolabeled SF/HGF. The factor stimulated tyrosine kinase activity of the transfected p190MET and induced changes in cell shape, migration in Boyden chambers, and invasion of collagen matrices in vitro. The motile and invasive phenotype was transient and strictly dependent on the presence of SF/HGF. The factor did not stimulate either cell growth or thymidine incorporation in transfected cells, while it promoted colony formation in soft agar in the presence of 5% fetal calf serum. These data show that, in the presence of its ligand, the MET receptor expressed in fibroblasts induces cells to pursue a motogenic-invasive rather than a proliferative program.

AB - The MET protooncogene encodes p190MET, a tyrosine kinase which is the receptor for a molecule known as scatter factor or hepatocyte growth factor (SF/HGF). This molecule has different biological activities, including stimulation of cell motility, promotion of matrix invasion and, in some cells, mitogenesis. We have cloned the full-length MET cDNA and transfected it into NIH 3T3 fibroblasts. Stable transfectants expressed the p190MET receptor together with two previously described truncated forms of 140 and 130 kDa lacking the tyrosine kinase domain. All three forms bound radiolabeled SF/HGF. The factor stimulated tyrosine kinase activity of the transfected p190MET and induced changes in cell shape, migration in Boyden chambers, and invasion of collagen matrices in vitro. The motile and invasive phenotype was transient and strictly dependent on the presence of SF/HGF. The factor did not stimulate either cell growth or thymidine incorporation in transfected cells, while it promoted colony formation in soft agar in the presence of 5% fetal calf serum. These data show that, in the presence of its ligand, the MET receptor expressed in fibroblasts induces cells to pursue a motogenic-invasive rather than a proliferative program.

KW - Invasion

KW - Tyrosine kinase receptors

UR - http://www.scopus.com/inward/record.url?scp=0027458940&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027458940&partnerID=8YFLogxK

M3 - Article

C2 - 8380644

AN - SCOPUS:0027458940

VL - 90

SP - 649

EP - 653

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 2

ER -