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Autocrine growth stimulation of human renal Wilms' tumour G401 cells by a gastrin-like peptide

✍ Scribed by Melanie Blackmore; Elaine Doherty; Janet E. Manning; Barry H. Hirst


Book ID
102865652
Publisher
John Wiley and Sons
Year
1994
Tongue
French
Weight
735 KB
Volume
57
Category
Article
ISSN
0020-7136

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✦ Synopsis


The role of gastrin in the control of growth of renal G40 I cells isolated from a human nephroblastoma (Wilms' tumour) was investigated. G401 cell growth was enhanced in the presence of exogenous gastrin. Addition of anti-gastrin antibodies to serumfree medium significantly inhibited the growth of G401 cells. G40 I cells contained the equivalent of 4.3 pg/ I O6 cells of gastrin, and serum-free medium collected over 48 hr from G401 cells contained the equivalent of 38 ng/IO6 cells of gastrin, as determined by radioimmunoassay. Growth of G401 cells was inhibited in a concentration-related way by a variety of gastrin/ CCK receptor antagonists. Devazepide and proglumide were, respectively, the most and the least potent inhibitors of G401 cell growth (potency order devazepide > L-365,260 = lorglumide > loxiglumide > benzotript > proglumide). These gastrin/CCK receptor antagonists had similar growth-inhibitory activities in human colonic adenocarcinoma HCT-I I6 cells. Growth of HCT-I I6 cells was stimulated to a lesser extent, as compared with G401 cells, by exogenous gastrin, and endogenous gastrin was not detectable in HCT-I I6 cells. The results are consistent with a role for a gastrin-like peptide in the control of growth of a renal cell line. The data suggest that gastrin/CCK receptor antagonists warrant further investigation as therapeutic agents for the control of gastrin-responsive tumours derived from outside, as well as inside, the gastrointestinal tract, including tumours derived from the kidney.


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