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

Progastrin1–80 stimulates growth of intestinal epithelial cells in vitro via high-affinity... Abstract 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 (rhPG 1–80 ) 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 CCK 1 and CCK 2 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 CCK 1 -R and CCK 2 -R on IEC cells. High-affinity ( K d = 0.5–1.0 nM) binding sites for 125 I-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 Footnotes Some of the studies presented in this manuscript have previously been presented in their preliminary form as an abstract ( 27 ). This work was supported by National Cancer Institute Grants CA-60087 and CA-72992 to P. Singh. Address for reprint requests and other correspondence: P. Singh, Dept. of Anatomy and Neurosciences, The Univ. of Texas Medical Branch, Galveston, TX 77555–1043 (E-mail: posingh@utmb.edu ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. First published October 16, 2002;10.1152/ajpgi.00351.2002 Copyright © 2003 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Gastrointestinal and Liver Physiology The American Physiological Society

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

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References (48)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1857
eISSN
1522-1547
DOI
10.1152/ajpgi.00351.2002
pmid
12388191
Publisher site
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Abstract

Abstract 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 (rhPG 1–80 ) 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 CCK 1 and CCK 2 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 CCK 1 -R and CCK 2 -R on IEC cells. High-affinity ( K d = 0.5–1.0 nM) binding sites for 125 I-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 Footnotes Some of the studies presented in this manuscript have previously been presented in their preliminary form as an abstract ( 27 ). This work was supported by National Cancer Institute Grants CA-60087 and CA-72992 to P. Singh. Address for reprint requests and other correspondence: P. Singh, Dept. of Anatomy and Neurosciences, The Univ. of Texas Medical Branch, Galveston, TX 77555–1043 (E-mail: posingh@utmb.edu ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. First published October 16, 2002;10.1152/ajpgi.00351.2002 Copyright © 2003 the American Physiological Society

Journal

AJP - Gastrointestinal and Liver Physiology – The American Physiological Society

Published: Feb 1, 2003

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