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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 immuno-reactivity of human colonic adenoma xenografts. (A) Western blots (±omeprazole treatment). (B) Densitometry scans of the immunoreactive bands generated from the Western blots. Red line: imunoreactive bands from grafts obtained from omeprazole-treated mice. Blue line: immuno reactive bands from grafts obtained from vehicle-treated mice.
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fig3: Western blot analysis showing CCK-2 receptor immuno-reactivity of human colonic adenoma xenografts. (A) Western blots (±omeprazole treatment). (B) Densitometry scans of the immunoreactive bands generated from the Western blots. Red line: imunoreactive bands from grafts obtained from omeprazole-treated mice. Blue line: immuno reactive bands from grafts obtained from vehicle-treated mice.

Mentions: Western blotting was performed on four xenografts from each experimental group. Each sample was a pool of two xenografts and each was loaded onto the gel at an equivalent protein concentration. The results are shown in Figure 3Figure 3


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 immuno-reactivity of human colonic adenoma xenografts. (A) Western blots (±omeprazole treatment). (B) Densitometry scans of the immunoreactive bands generated from the Western blots. Red line: imunoreactive bands from grafts obtained from omeprazole-treated mice. Blue line: immuno reactive bands from grafts obtained from vehicle-treated mice.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Western blot analysis showing CCK-2 receptor immuno-reactivity of human colonic adenoma xenografts. (A) Western blots (±omeprazole treatment). (B) Densitometry scans of the immunoreactive bands generated from the Western blots. Red line: imunoreactive bands from grafts obtained from omeprazole-treated mice. Blue line: immuno reactive bands from grafts obtained from vehicle-treated mice.
Mentions: Western blotting was performed on four xenografts from each experimental group. Each sample was a pool of two xenografts and each was loaded onto the gel at an equivalent protein concentration. The results are shown in Figure 3Figure 3

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