PMID- 12670907
OWN - NLM
STAT- MEDLINE
DCOM- 20030422
LR  - 20171116
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 63
IP  - 7
DP  - 2003 Apr 1
TI  - Hepatocyte growth factor/scatter factor induces feedback up-regulation of CD44v6 
      in melanoma cells through Egr-1.
PG  - 1576-82
AB  - The hepatocyte growth factor/scatter factor (HGF/SF) receptor c-Met and variants 
      of the CD44 family of surface adhesion molecules, including CD44v6, have been 
      implicated in cancer progression and metastasis. CD44 isoforms bearing heparin 
      sulfate chains can bind to HGF/SF and facilitate its presentation to c-Met. Here, 
      we demonstrate that HGF/SF-Met binding up-regulates the expression of CD44v6 in 
      murine melanoma cells, serving to compensate for loss by internalization. 
      c-Met-mediated CD44v6 up-regulation was achieved through transcriptional 
      activation of the immediate early gene egr-1. Enhanced egr-1 expression was 
      apparent at the level of RNA 40 min after exposure to HGF/SF, and Egr-1 protein 
      was detectable between 1 and 2 h post-treatment. CD44v6 RNA levels were 
      correspondingly elevated 2 h after HGF/SF exposure. HGF/SF induced egr-1 
      activation via the Ras>Erk1/2 pathway but not through either phosphatidylinositol 
      3'-kinase or protein kinase C. Binding of NK2, a naturally occurring splice 
      variant of HGF/SF, to c-Met failed to induce either Egr-1 or CD44v6, accounting 
      at least in part for its antagonistic behavior. We also identified an 
      Egr-1-binding site in the mouse CD44 gene promoter that accounts for its 
      responsiveness to HGF/SF in melanoma cells. The compensatory up-regulation of 
      both c-Met and CD44v6 in response to HGF/SF has important implications with 
      respect to strategies used by cancer cells to sustain stimulation of growth- and 
      metastasis-promoting pathways associated with tumor progression.
FAU - Recio, Juan A
AU  - Recio JA
AD  - Laboratory of Molecular Biology, National Cancer Institute, National Institutes 
      of Health, Bethesda, Maryland 20892-4264, USA.
FAU - Merlino, Glenn
AU  - Merlino G
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (CD44v6 antigen)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Egr1 protein, mouse)
RN  - 0 (Glycoproteins)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - Base Sequence
MH  - DNA-Binding Proteins/biosynthesis/genetics/*physiology
MH  - Early Growth Response Protein 1
MH  - Feedback/physiology
MH  - Gene Expression Regulation, Neoplastic
MH  - Glycoproteins/*biosynthesis/genetics/immunology
MH  - Hepatocyte Growth Factor/*physiology
MH  - Hyaluronan Receptors/*biosynthesis/genetics/immunology
MH  - *Immediate-Early Proteins
MH  - MAP Kinase Signaling System/immunology
MH  - Melanoma, Experimental/genetics/*immunology/metabolism
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Molecular Sequence Data
MH  - Promoter Regions, Genetic
MH  - Protein Structure, Tertiary
MH  - Proto-Oncogene Proteins c-met/immunology/metabolism
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Transcription Factors/biosynthesis/genetics/*physiology
MH  - Transcriptional Activation
MH  - Up-Regulation
EDAT- 2003/04/03 05:00
MHDA- 2003/04/23 05:00
CRDT- 2003/04/03 05:00
PHST- 2003/04/03 05:00 [pubmed]
PHST- 2003/04/23 05:00 [medline]
PHST- 2003/04/03 05:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2003 Apr 1;63(7):1576-82.