Skip to main content
NCBI home page
Journal of Cancer Research and Clinical Oncology logoLink to Journal of Cancer Research and Clinical Oncology
. 1995 Nov;121(11):661–666. doi: 10.1007/BF01218524

Expression of gastrin, gastrin/CCK-B and gastrin/CCK-C receptors in human colorectal carcinomas

A Imdahl 1,✉, T Mantamadiotis 2, S Eggstein 1, E H Farthmann 1, G S Baldwin 2
PMCID: PMC12200323  PMID: 7593130

Abstract

To investigate further the presence of an autocrine proliferative loop involving gastrin in colorectal carcinomas and to clarify the receptor responsible, 102 human colorectal carcinomas and 10 hepatic metastases were investigated for the expression of the genes encoding gastrin, the gastrin/CCK-B receptor and the gastrin/CCK-C receptor. Levels of RNA expression were assayed by RNase protection assay. In addition, gastrin/CCK receptors on crude membranes of tumour tissue were assayed by radioligand binding. High-affinity gastrin/CCK-B receptors were not detected in any of the carcinomas investigated, whereas in 36% low-affinity binding was observed, consistent with the expression of the gastrin/CCK-C receptor. RNase protection assay detected the RNA for the gastrin/CCK-B receptor in 11% of the carcinomas investigated, whereas the RNA for the gastrin/CCK-C receptor was demonstrated in 75% and the RNA for gastrin in 86% of the carcinomas investigated. These results confirm the recent demonstration of progastrin fragments in colorectal carcinomas. One possible explanation for progastrin expression is that such progastrin fragments may participate in an autocrine proliferative loop. The receptor involved in this loop is more likely to be the low-affinity gastrin/CCK-C receptor rather than the gastrin/CCK-B receptor, which is rarely expressed in colorectal carcinomas.

Key words: Colorectal carcinoma, Gastrin, Gastrin-binding protein, Gastrin/CCK-B receptor, RNase protection assay

References

  1. Baldwin GS (1994) anti-proliferative gastrin/cholecystokinin receptor receptor antagonists target the 78 kDa gastrin-binding protein. Proc Natl Acad Sci USA 91: 7593–7597 [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baldwin GS (1995) The 78 kDa gastrin-binding protein is a candidate receptor for autocrine progastrin. FEBS Lett (in press) [DOI] [PubMed]
  3. Baldwin GS, Zhang Q-X (1992) Measurement of gastrin and transforming growth factor messenger RNA levels in colon carcinoma cell lines by quantitative polymerase chain reaction. Cancer Res 52: 2261–2267 [PubMed] [Google Scholar]
  4. Boel E, Vuust J, Norris F, Norris K, Wind A, Rehfeld JF, Marcker KA (1983) Molecular cloning of human gastrin cDNA: evidence for evolution of gastrin by gene duplication. Proc Natl Acad Sci USA 80: 2866–2869 [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bold RJ, Ishizuka J, Townsend CM and Thompson JC (1994) Gastrin stimulates growth of human colon cancer cells via a receptor other than CCK-A or CCK-B. Biochem Biophys Res Commun 202: 1222–1226 [DOI] [PubMed] [Google Scholar]
  6. Chomczynski P, Sacchi N (1987) Single step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159 [DOI] [PubMed] [Google Scholar]
  7. Finley GG, Koski RA, Melhem MF, Pipas JM, Meisler AI (1993) Expression of the gastrin gene in the normal human colon and colorectal carcinoma. Cancer Res 53: 2919–2926 [PubMed] [Google Scholar]
  8. Frucht H, Gazdar AF, Park J-A, Oie H, Jensen RT (1992) Characterization of functional receptors for gastrointestinal hormones on human colon cancer cells. Cancer Res 52: 1114–1122 [PubMed] [Google Scholar]
  9. Hoosein NM, Kiener PA, Curry RC, Rovati LC, McGilbra DK, Brattain MG (1988) Antiproliferative effects of gastrin receptor antagonists and antibodies to gastrin on human colon carcinom cell lines. Cancer Res 48: 7179–7183 [PubMed] [Google Scholar]
  10. Imdahl A, Michalski Y, Eggstein S, Strik M, Farthmann EH (1992) Serum Gastrin Konzentration bei Patienten mit einem kolorektalen Karzinom oder Adenom. Zentralbl Chir 117: 439–443 [PubMed] [Google Scholar]
  11. Kameyama M, Fukuda I, Imaoka S, Nakamori S, Iwanga T (1993) Level of serum gastrin as a predictor of liver metastasis from colorectal cancer. Dis Colon Rectum 36: 497–500 [DOI] [PubMed] [Google Scholar]
  12. Matsushima Y, Kinoshita Y, Nakata H, Inomoto-Naribayashi Y, Asahara M, Kawanami C, Nakamura A, Ito M, Matui T, Fujiwara T, Watanabe H, Chiba T (1994) Gastrin receptor gene expression in several human carcinomas. Jpn J Cancer Res 85: 819–824 [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Melton DA, Krieg PA, Rebagliati MR, Maniatis T, Zinn K, Green MR (1984) Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promotor. Nucleic Acids Res 12: 7035–7056 [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nemeth J, Taylor B, Pauwels S, Varro A, Dockray GJ (1993) Identification of progastrin derived peptides in colorectal carcinoma extracts. Gut 34: 90–95 [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pisegna JR, deWerth A, Huppi K, Wank SA (1992) Molecular cloning of the human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal expression. Biochem Biophys Res Commun 189: 296–303 [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Seitz JF, Giovanni M, Gouvernet J, Gauthier AP (1991) Elevated serum gastrin levels in patients with colorectal neoplasia. J Clin Gastroenterol 13: 541–545 [DOI] [PubMed] [Google Scholar]
  17. Seva C, Dickinson CJ, Yamada T (1994) Growth-promoting effects of glycine-extended progastrin. Science 265: 410–412 [DOI] [PubMed] [Google Scholar]
  18. Singh P, Townsend MC, Singh H, Rubin N, Thompson JC (1987) Gastrin receptors in normal and neoplastic gastrointestinal mucosa. In: Bali JP, Martinez J (eds) Gastrin and cholecystokinin. Excerpta Medica, Amsterdam, pp 99–111 [Google Scholar]
  19. Smith JP, Wood JG, Solomon TE (1989) Elevated gastrin levels in patients with colon cancer of adenomatous polyps. Dig Dis Sci 34: 171–174 [DOI] [PubMed] [Google Scholar]
  20. Suzuki H, Matsumoto K, Terashima H (1988) Serum levels of gastrin in patients with colorectal neoplasia. Dis Colon Rectum 31: 716–717 [DOI] [PubMed] [Google Scholar]
  21. Thumwood CM, Ji H, Baldwin GS (1991) Inhibition of cell proliferation by the cholecystokinin antagonist L-364, 718. Exp Cell Res 192: 189–192 [DOI] [PubMed] [Google Scholar]
  22. Upp RH, Singh P, Townsend MC, Thompson JC (1989) Clinical significance of gastrin receptors in human colon cancer. Cancer Res 49: 488–492 [PubMed] [Google Scholar]
  23. Van Solinge WW, Nielsen FC, Friis-Hansen L, Falkmer UG, Rehfeld JF (1993) Expression but incomplete maturation of progastrin in colorectal carcinomas. Gastroenterology 104: 1099–1107 [DOI] [PubMed] [Google Scholar]
  24. Watson SA, Durrant LG, Wencyk PM, Watson AL, Morris DL (1991) Intracellular gastrin in human gastrointestinal tumor cells. J Natl Cancer Inst 83: 866–871 [DOI] [PubMed] [Google Scholar]
  25. Weinstock J, Baldwin GS (1988) Binding of gastrin17 to human gastric carcinoma cell lines. Cancer Res 48: 932–937 [PubMed] [Google Scholar]
  26. Yapp R, Modin IM, Kumar RR, Binder HJ, Dubrow R (1992) Gastrin and colorectal cancer Evidence against an association. Dig Dis Sci 37: 481–484 [DOI] [PubMed] [Google Scholar]
  27. Zhou W, Povoski SP, Longnecker DS, Bell RH (1992) Novel expression of gastrin (cholecystokinin B) receptors in azaserine induced rat pancreatic carcinoma: receptor determinatin and characterization. Cancer Res 52: 6905–6911 [PubMed] [Google Scholar]

Articles from Journal of Cancer Research and Clinical Oncology are provided here courtesy of Springer

RESOURCES