Abstract
The possible production of gastrin by colorectal carcinomas has been studied. Extracts of 44 tumours and adjacent macroscopically normal tissue were examined in radioimmunoassay using the following antibodies: (i) L289 raised to a C-terminal fragment of progastrin which shows specificity for intact progastrin, but not the extreme C-terminal tryptic peptide; (ii) LW60 raised to a C-terminal fragment of progastrin which reacts with progastrin and its C-terminal tryptic peptide; (iii) 109-21 which was raised to, and reacts with, Gly-extended forms of heptadecapeptide gastrin--that is, biosynthetic intermediates on the pathway producing active gastrin; and (iv) L2 which reacts with amidated, biologically active gastrins. All samples contained detectable material in assays using LW60; in general, concentrations measured with this antibody were higher than with the other antibodies, and in particular there were higher concentrations in tumour compared with normal tissue extracts. Tumour extracts also contained higher concentrations of immunoreactivity compared with normal tissue, in assays using antibodies L289 and 109-21. In contrast, amidated gastrins were found in similar concentrations in tumour and normal tissue, and concentrations were the lowest of those recorded in the four assays. Separation on Sephadex G50 revealed peaks compatible with progastrin and its C-terminal flanking peptide, and two other peaks that are so far unidentified. In conclusion most colorectal carcinomas contain peptides derived from the gastrin precursor, progastrin, but for the most part these tumours do not convert progastrin into biologically active products.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Azuma T., Taggart R. T., Walsh J. H. Effects of bombesin on the release of glycine-extended progastrin (gastrin G) in rat antral tissue culture. Gastroenterology. 1987 Aug;93(2):322–329. doi: 10.1016/0016-5085(87)91022-5. [DOI] [PubMed] [Google Scholar]
- Baldwin G. S., Casey A., Mantamadiotis T., McBride K., Sizeland A. M., Thumwood C. M. PCR cloning and sequence of gastrin mRNA from carcinoma cell lines. Biochem Biophys Res Commun. 1990 Jul 31;170(2):691–697. doi: 10.1016/0006-291x(90)92146-q. [DOI] [PubMed] [Google Scholar]
- Beauchamp R. D., Townsend C. M., Jr, Singh P., Glass E. J., Thompson J. C. Proglumide, a gastrin receptor antagonist, inhibits growth of colon cancer and enhances survival in mice. Ann Surg. 1985 Sep;202(3):303–309. doi: 10.1097/00000658-198509000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Desmond H., Pauwels S., Varro A., Gregory H., Young J., Dockray G. J. Isolation and characterization of the intact gastrin precursor from a gastrinoma. FEBS Lett. 1987 Jan 5;210(2):185–188. doi: 10.1016/0014-5793(87)81334-0. [DOI] [PubMed] [Google Scholar]
- Dockray G. J., Best L., Taylor I. L. Immunochemical characterization of gastrin in pancreatic islets of normal and genetically obese mice. J Endocrinol. 1977 Feb;72(2):143–151. doi: 10.1677/joe.0.0720143. [DOI] [PubMed] [Google Scholar]
- Guo Y. S., Baijal M., Jin G. F., Thompson J. C., Townsend C. M., Jr, Singh P. Growth-promoting effects of gastrin on mouse colon cancer cells in vitro: absence of autocrine effects. In Vitro Cell Dev Biol. 1990 Sep;26(9):871–877. doi: 10.1007/BF02624612. [DOI] [PubMed] [Google Scholar]
- Hoosein N. M., Kiener P. A., Curry R. C., Brattain M. G. Evidence for autocrine growth stimulation of cultured colon tumor cells by a gastrin/cholecystokinin-like peptide. Exp Cell Res. 1990 Jan;186(1):15–21. doi: 10.1016/0014-4827(90)90204-n. [DOI] [PubMed] [Google Scholar]
- Kusyk C. J., McNiel N. O., Johnson L. R. Stimulation of growth of a colon cancer cell line by gastrin. Am J Physiol. 1986 Nov;251(5 Pt 1):G597–G601. doi: 10.1152/ajpgi.1986.251.5.G597. [DOI] [PubMed] [Google Scholar]
- Pauwels S., Desmond H., Dimaline R., Dockray G. J. Identification of progastrin in gastrinomas, antrum, and duodenum by a novel radioimmunoassay. J Clin Invest. 1986 Feb;77(2):376–381. doi: 10.1172/JCI112315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rahier J., Pauwels S., Dockray G. J. Biosynthesis of gastrin. Localization of the precursor and peptide products using electron microscopic-immunogold methods. Gastroenterology. 1987 May;92(5 Pt 1):1146–1152. [PubMed] [Google Scholar]
- Singh P., Rae-Venter B., Townsend C. M., Jr, Khalil T., Thompson J. C. Gastrin receptors in normal and malignant gastrointestinal mucosa: age-associated changes. Am J Physiol. 1985 Dec;249(6 Pt 1):G761–G769. doi: 10.1152/ajpgi.1985.249.6.G761. [DOI] [PubMed] [Google Scholar]
- Smith J. P., Solomon T. E. Effects of gastrin, proglumide, and somatostatin on growth of human colon cancer. Gastroenterology. 1988 Dec;95(6):1541–1548. doi: 10.1016/s0016-5085(88)80075-1. [DOI] [PubMed] [Google Scholar]
- Smith J. P., Wood J. G., Solomon T. E. Elevated gastrin levels in patients with colon cancer or adenomatous polyps. Dig Dis Sci. 1989 Feb;34(2):171–174. doi: 10.1007/BF01536047. [DOI] [PubMed] [Google Scholar]
- Townsend C. M., Jr, Beauchamp R. D., Singh P., Thompson J. C. Growth factors and intestinal neoplasms. Am J Surg. 1988 Mar;155(3):526–536. doi: 10.1016/s0002-9610(88)80128-4. [DOI] [PubMed] [Google Scholar]
- Varro A., Desmond H., Pauwels S., Gregory H., Young J., Dockray G. J. The human gastrin precursor. Characterization of phosphorylated forms and fragments. Biochem J. 1988 Dec 15;256(3):951–957. doi: 10.1042/bj2560951. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watson S. A., Durrant L. G., Wencyk P. M., Watson A. L., Morris D. L. Intracellular gastrin in human gastrointestinal tumor cells. J Natl Cancer Inst. 1991 Jun 19;83(12):866–871. doi: 10.1093/jnci/83.12.866. [DOI] [PubMed] [Google Scholar]
- Winsett O. E., Townsend C. M., Jr, Glass E. J., Thompson J. C. Gastrin stimulates growth of colon cancer. Surgery. 1986 Mar;99(3):302–307. [PubMed] [Google Scholar]
- Wong K., Beardshall K., Waters C. M., Calam J., Poston G. J. Postprandial hypergastrinaemia in patients with colorectal cancer. Gut. 1991 Nov;32(11):1352–1354. doi: 10.1136/gut.32.11.1352. [DOI] [PMC free article] [PubMed] [Google Scholar]