PMID- 11971760
OWN - NLM
STAT- MEDLINE
DCOM- 20020924
LR  - 20181113
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 365
IP  - Pt 3
DP  - 2002 Aug 1
TI  - Gastrin-stimulated gastric epithelial cell invasion: the role and mechanism of 
      increased matrix metalloproteinase 9 expression.
PG  - 873-9
AB  - The gastric hormone gastrin regulates the organization of the gastric epithelium, 
      but the cellular control mechanisms are yet unknown. Epithelial remodelling 
      typically involves extracellular proteolysis mediated by the matrix 
      metalloproteinases (MMPs). Since a gene-array analysis of the gastric cancer cell 
      line AGS-G(R) suggested that gastrin increased MMP-9 expression, we examined the 
      control of MMP-9 expression by gastrin. Gelatin zymography confirmed gastrin 
      induction of MMP-9 in AGS-G(R) cells, but showed a small inhibition of MMP-2. 
      Immunocytochemical studies showed that MMP-9 was localized to vesicles that 
      appeared to traffic along the processes that were extended in response to 
      gastrin. Gastrin stimulated the invasion of AGS-G(R) cells through artificial 
      basement membrane, which was reduced by an inhibitor of MMP-2/-9. There was also 
      an increase in MMP-9 in the stomach of patients with elevated plasma gastrin and 
      multiple-endocrine neoplasia type 1 (MEN-1) syndrome, suggesting in vivo 
      regulation of MMP-9 expression by gastrin. Finally, we showed that the expression 
      of 1.9 kb of human MMP-9 gene promoter coupled with luciferase (MMP-9-luc) was 
      increased 7.65+/-1.2-fold by gastrin, via a pathway which includes stimulation of 
      protein kinase C, and activation of Raf and the mitogen-activated protein (MAP) 
      kinase pathway. The tumour suppressor menin (which is mutated in MEN-1 syndrome) 
      inhibited the expression of MMP-9-luc by gastrin. These results suggest that 
      gastrin increases MMP-9 expression, which is associated with increased invasion, 
      and this is a putative mechanism regulating remodelling of the gastric 
      epithelium.
FAU - Wroblewski, Lydia E
AU  - Wroblewski LE
AD  - Physiological Laboratory, University of Liverpool, Crown Street, Liverpool L69 
      3BX, U.K.
FAU - Pritchard, David M
AU  - Pritchard DM
FAU - Carter, Stuart
AU  - Carter S
FAU - Varro, Andrea
AU  - Varro A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Gastrins)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factor AP-1)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Carcinoid Tumor/enzymology/pathology
MH  - Epithelial Cells/*metabolism
MH  - Female
MH  - Gastric Mucosa/cytology/*metabolism/pathology
MH  - Gastrins/*metabolism
MH  - Gene Expression Regulation, Enzymologic
MH  - Genes, Reporter
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinase 9/genetics/*metabolism
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/physiopathology
MH  - Neoplasm Invasiveness
MH  - Neoplasm Proteins/metabolism
MH  - *Proto-Oncogene Proteins
MH  - Recombinant Fusion Proteins/metabolism
MH  - Transcription Factor AP-1/metabolism
MH  - Tumor Cells, Cultured
PMC - PMC1222716
EDAT- 2002/04/25 10:00
MHDA- 2002/09/25 06:00
PMCR- 2003/02/01
CRDT- 2002/04/25 10:00
PHST- 2002/04/24 00:00 [accepted]
PHST- 2002/03/22 00:00 [revised]
PHST- 2002/01/10 00:00 [received]
PHST- 2002/04/25 10:00 [pubmed]
PHST- 2002/09/25 06:00 [medline]
PHST- 2002/04/25 10:00 [entrez]
PHST- 2003/02/01 00:00 [pmc-release]
AID - BJ20020068 [pii]
AID - 10.1042/BJ20020068 [doi]
PST - ppublish
SO  - Biochem J. 2002 Aug 1;365(Pt 3):873-9. doi: 10.1042/BJ20020068.