PMID- 17101322
OWN - NLM
STAT- MEDLINE
DCOM- 20061212
LR  - 20181101
IS  - 0016-5085 (Print)
IS  - 0016-5085 (Linking)
VI  - 131
IP  - 5
DP  - 2006 Nov
TI  - Production, secretion, and biological activity of the C-terminal flanking peptide 
      of human progastrin.
PG  - 1463-74
AB  - BACKGROUND & AIMS: Processing of progastrin, the 80-amino acid precursor of the 
      hormone gastrin, generates a variety of peptides with distinct distributions and 
      biological activities. However, little is known regarding the expression, 
      secretion, and biological activity of the 6-amino acid C-terminal flanking 
      peptide (CTFP) of progastrin. The objectives were to determine the concentration 
      of CTFP in normal subjects and patients with gastrointestinal diseases and to 
      investigate the biological activity of CTFP. METHODS: CTFP, gastrin-amide 
      (Gamide), glycine-extended gastrin (Ggly), and progastrin were measured using 
      region-specific radioimmunoassay (RIA) in antral extracts and resected colorectal 
      cancers (CRC) and in plasma from normal subjects (fasting and meal stimulated) 
      and from patients with CRC, multiple endocrine neoplasia type 1 (MEN-1), or 
      pernicious anemia. The effect of CTFP on proliferation, migration, and activation 
      of the mitogen-activated protein kinase (MAPK) pathway in several types of 
      gastrointestinal cell lines was determined. RESULTS: CTFP is by far the 
      predominant progastrin-derived peptide found in the antrum (4-fold higher than 
      Gamide), resected CRC, and circulation (60-fold higher than Gamide) and is 
      released after meal stimulation. The hypergastrinemic patients (MEN-1, pernicious 
      anemia) had elevated plasma Gamide but unaltered CTFP demonstrating differential 
      secretion of these 2 progastrin-derived peptides. Finally, CTFP stimulated 
      proliferation and migration and activated MAPK of cells in culture. CONCLUSIONS: 
      The high and regulated expression of CTFP in healthy and diseased subjects 
      combined with the evidence for biological activity of CTFP demonstrates that CTFP 
      is not an inactive metabolite of progastrin processing but is a bioactive peptide 
      with potential roles in the normal and diseased gastrointestinal tract.
FAU - Smith, Kelly A
AU  - Smith KA
AD  - Department of Surgery, University of Melbourne, Austin Health, Heidelberg, 
      Victoria, Australia.
FAU - Patel, Oneel
AU  - Patel O
FAU - Lachal, Shamilah
AU  - Lachal S
FAU - Jennings, Ian
AU  - Jennings I
FAU - Kemp, Bruce
AU  - Kemp B
FAU - Burgess, John
AU  - Burgess J
FAU - Baldwin, Graham S
AU  - Baldwin GS
FAU - Shulkes, Arthur
AU  - Shulkes A
LA  - eng
GR  - R01 GM065926/GM/NIGMS NIH HHS/United States
GR  - R01 GM065926-04A1/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060822
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (Gastrins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Protein Precursors)
RN  - 3BL184GALN (big gastrin)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
CIN - Gastroenterology. 2006 Nov;131(5):1638-40. PMID: 17101333
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Colorectal Neoplasms/blood
MH  - Gastrins/*biosynthesis/blood/pharmacology
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Peptide Fragments/*biosynthesis/pharmacology
MH  - Phosphorylation
MH  - Protein Precursors/*biosynthesis/blood/pharmacology
MH  - Pyloric Antrum/metabolism
EDAT- 2006/11/15 09:00
MHDA- 2006/12/13 09:00
CRDT- 2006/11/15 09:00
PHST- 2005/12/21 00:00 [received]
PHST- 2006/07/12 00:00 [accepted]
PHST- 2006/11/15 09:00 [pubmed]
PHST- 2006/12/13 09:00 [medline]
PHST- 2006/11/15 09:00 [entrez]
AID - S0016-5085(06)01800-2 [pii]
AID - 10.1053/j.gastro.2006.08.040 [doi]
PST - ppublish
SO  - Gastroenterology. 2006 Nov;131(5):1463-74. doi: 10.1053/j.gastro.2006.08.040. 
      Epub 2006 Aug 22.