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Potential role of endocrine gastrin in the colonic adenoma carcinoma sequence.

Watson SA, Morris TM, McWilliams DF, Harris J, Evans S, Smith A, Clarke PA - Br. J. Cancer (2002)

Bottom Line: CCK-2 receptor blockade was achieved by using neutralising antiserum.Omeprazole and lansoprazole-induced hyper-gastrinaemia (resulting in serum gastrin levels of 34.0 and 153.0 pM, respectively) significantly increased the weight of the human adenoma grafts (43% (P=0.016) and 70% (P=0.014), respectively).The effect of hypergastrinaemia on tumour growth was reversed by use of antiserum directed against the CCK-2 receptor.

View Article: PubMed Central - PubMed

Affiliation: Academic Unit of Cancer Studies, University of Nottingham, Nottingham, NG7 2UH, UK. sue.watson@nottingham.ac.uk

ABSTRACT
The role of hyper-gastrinaemia in the incidence of colonic cancer remains to be clarified. The aim of this study was to determine whether cholecystokinin-2 (CCK-2) receptor expression predicts the sensitivity of human colonic adenomas to the proliferative effects of serum hyper-gastrinaemia. Gene expression of the classical (74 kDa) CCK-2 receptor in human colonic adenoma specimens and cell lines, was quantified by real-time PCR. Western blotting, using a CCK-2 receptor antiserum, confirmed protein expression. A transformed human colonic adenoma was grown in SCID mice, with hyper-gastrinaemia induced by proton pump inhibitors. CCK-2 receptor blockade was achieved by using neutralising antiserum. Both human colonic adenoma cell lines and biopsies expressed CCK-2 receptor mRNA at levels comparable with CCK-2 receptor transfected fibroblasts and oxyntic mucosa. Western blotting confirmed immunoreactive CCK-2 receptor bands localised to 45, 74 and 82.5 kDa. Omeprazole and lansoprazole-induced hyper-gastrinaemia (resulting in serum gastrin levels of 34.0 and 153.0 pM, respectively) significantly increased the weight of the human adenoma grafts (43% (P=0.016) and 70% (P=0.014), respectively). The effect of hypergastrinaemia on tumour growth was reversed by use of antiserum directed against the CCK-2 receptor. Hyper-gastrinaemia may promote proliferation of human colonic adenomas that express CCK-2 receptor isoforms.

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Related in: MedlinePlus

Western blot analysis showing CCK-2 receptor isoform immuno-reactivity of human colonic adenoma specimens and human colonic adenoma cell lines. (A) Human colonic adenoma cell lines. (B) Human colonic adenoma specimens. Resection margin normal (N), adenoma (A) and adenocarcinoma (C) specimens from individual patients. (C) Human colonic adenocarcinoma specimens. Resection margin normal (N) and adenocarcinoma (C) specimens from individual patients.
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fig2: Western blot analysis showing CCK-2 receptor isoform immuno-reactivity of human colonic adenoma specimens and human colonic adenoma cell lines. (A) Human colonic adenoma cell lines. (B) Human colonic adenoma specimens. Resection margin normal (N), adenoma (A) and adenocarcinoma (C) specimens from individual patients. (C) Human colonic adenocarcinoma specimens. Resection margin normal (N) and adenocarcinoma (C) specimens from individual patients.

Mentions: Using the GRE1 antiserum, an immunoreactive band at the 74‚ÄČkDa molecular weight was expressed by the human adenoma cell lines (Figure 2AFigure 2


Potential role of endocrine gastrin in the colonic adenoma carcinoma sequence.

Watson SA, Morris TM, McWilliams DF, Harris J, Evans S, Smith A, Clarke PA - Br. J. Cancer (2002)

Western blot analysis showing CCK-2 receptor isoform immuno-reactivity of human colonic adenoma specimens and human colonic adenoma cell lines. (A) Human colonic adenoma cell lines. (B) Human colonic adenoma specimens. Resection margin normal (N), adenoma (A) and adenocarcinoma (C) specimens from individual patients. (C) Human colonic adenocarcinoma specimens. Resection margin normal (N) and adenocarcinoma (C) specimens from individual patients.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376163&req=5

fig2: Western blot analysis showing CCK-2 receptor isoform immuno-reactivity of human colonic adenoma specimens and human colonic adenoma cell lines. (A) Human colonic adenoma cell lines. (B) Human colonic adenoma specimens. Resection margin normal (N), adenoma (A) and adenocarcinoma (C) specimens from individual patients. (C) Human colonic adenocarcinoma specimens. Resection margin normal (N) and adenocarcinoma (C) specimens from individual patients.
Mentions: Using the GRE1 antiserum, an immunoreactive band at the 74‚ÄČkDa molecular weight was expressed by the human adenoma cell lines (Figure 2AFigure 2

Bottom Line: CCK-2 receptor blockade was achieved by using neutralising antiserum.Omeprazole and lansoprazole-induced hyper-gastrinaemia (resulting in serum gastrin levels of 34.0 and 153.0 pM, respectively) significantly increased the weight of the human adenoma grafts (43% (P=0.016) and 70% (P=0.014), respectively).The effect of hypergastrinaemia on tumour growth was reversed by use of antiserum directed against the CCK-2 receptor.

View Article: PubMed Central - PubMed

Affiliation: Academic Unit of Cancer Studies, University of Nottingham, Nottingham, NG7 2UH, UK. sue.watson@nottingham.ac.uk

ABSTRACT
The role of hyper-gastrinaemia in the incidence of colonic cancer remains to be clarified. The aim of this study was to determine whether cholecystokinin-2 (CCK-2) receptor expression predicts the sensitivity of human colonic adenomas to the proliferative effects of serum hyper-gastrinaemia. Gene expression of the classical (74 kDa) CCK-2 receptor in human colonic adenoma specimens and cell lines, was quantified by real-time PCR. Western blotting, using a CCK-2 receptor antiserum, confirmed protein expression. A transformed human colonic adenoma was grown in SCID mice, with hyper-gastrinaemia induced by proton pump inhibitors. CCK-2 receptor blockade was achieved by using neutralising antiserum. Both human colonic adenoma cell lines and biopsies expressed CCK-2 receptor mRNA at levels comparable with CCK-2 receptor transfected fibroblasts and oxyntic mucosa. Western blotting confirmed immunoreactive CCK-2 receptor bands localised to 45, 74 and 82.5 kDa. Omeprazole and lansoprazole-induced hyper-gastrinaemia (resulting in serum gastrin levels of 34.0 and 153.0 pM, respectively) significantly increased the weight of the human adenoma grafts (43% (P=0.016) and 70% (P=0.014), respectively). The effect of hypergastrinaemia on tumour growth was reversed by use of antiserum directed against the CCK-2 receptor. Hyper-gastrinaemia may promote proliferation of human colonic adenomas that express CCK-2 receptor isoforms.

Show MeSH
Related in: MedlinePlus