AJP - GI Information on EB 2010
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol 284: G328-G339, 2003. First published October 16, 2002; doi:10.1152/ajpgi.00351.2002
0193-1857/03 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
284/2/G328    most recent
00351.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (30)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Singh, P.
Right arrow Articles by Owlia, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Singh, P.
Right arrow Articles by Owlia, A.
Vol. 284, Issue 2, G328-G339, February 2003

Progastrin1-80 stimulates growth of intestinal epithelial cells in vitro via high-affinity binding sites

P. Singh1, X. Lu2, S. Cobb1, B. T. Miller1, N. Tarasova4, A. Varro3, and A. Owlia1

1 Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston, Texas 77555-1043; 2 Elim Biopharmaceuticals, South San Francisco, California 94080; 3 Department of Physiology, University of Liverpool, Liverpool L69 3BX, United Kingdom; and 4 National Cancer Institute, Fredericksburg, Maryland 21702

Proliferation and carcinogenesis of the large intestinal epithelial cells (IEC) cells is significantly increased in transgenic mice that overexpress the precursor progastrin (PG) peptide. It is not known if the in vivo growth effects of PG on IEC cells are mediated directly or indirectly. Full-length recombinant human PG (rhPG1-80) was generated to examine possible direct effects of PG on IEC cells. Surprisingly, rhPG (0.1-1.0 nM) was more effective than the completely processed gastrin 17 (G17) peptide as a growth factor. Even though IEC cells did not express CCK1 and CCK2 receptors (-R), fluorescently labeled G17 and Gly-extended G17 (G-Gly) were specifically bound to the cells, suggesting the presence of binding proteins other than CCK1-R and CCK2-R on IEC cells. High-affinity (Kd = 0.5-1.0 nM) binding sites for 125I-rhPG were discovered on IEC cells that demonstrated relative binding affinity for gastrin-like peptides in the order PG >=  COOH-terminally extended G17 >=  G-Gly > G17 > *CCK-8 (* significant difference; P < 0.05). In conclusion, our studies demonstrate for the first time direct growth effects of the full-length precursor peptide on IEC cells in vitro that are apparently mediated by the high-affinity PG binding sites that were discovered on these cells.

progastrin-preferring receptors; confocal microscopy; in vitro growth effects; Gly-gastrin


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
S. Umar, S. Sarkar, Y. Wang, and P. Singh
Functional Cross-talk between {beta}-Catenin and NF{kappa}B Signaling Pathways in Colonic Crypts of Mice in Response to Progastrin
J. Biol. Chem., August 14, 2009; 284(33): 22274 - 22284.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. Rengifo-Cam, S. Umar, S. Sarkar, and P. Singh
Antiapoptotic Effects of Progastrin on Pancreatic Cancer Cells Are Mediated by Sustained Activation of Nuclear Factor-{kappa}B
Cancer Res., August 1, 2007; 67(15): 7266 - 7274.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
M. Dufresne, C. Seva, and D. Fourmy
Cholecystokinin and gastrin receptors.
Physiol Rev, July 1, 2006; 86(3): 805 - 847.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Ferrand, C. Bertrand, G. Portolan, G. Cui, J. Carlson, L. Pradayrol, D. Fourmy, M. Dufresne, T. C. Wang, and C. Seva
Signaling Pathways Associated with Colonic Mucosa Hyperproliferation in Mice Overexpressing Gastrin Precursors
Cancer Res., April 1, 2005; 65(7): 2770 - 2777.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
H. Wu, A. Owlia, and P. Singh
Precursor peptide progastrin1-80 reduces apoptosis of intestinal epithelial cells and upregulates cytochrome c oxidase Vb levels and synthesis of ATP
Am J Physiol Gastrointest Liver Physiol, December 1, 2003; 285(6): G1097 - G1110.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online