Expression of progastrin-derived peptides and gastrin receptors in a panel of gastrointestinal carcinoma cell lines.
To assess the potential of gastrin receptor antagonists in the treatment of gastrointestinal cancer, the presence of an autocrine loop involving progastrin-derived peptides has been investigated in two colorectal and one gastric carcinoma cell lines. Progastrin, glycine-extended gastrin and amidated gastrin were detected in cell extracts or conditioned media by radio-immunoassay. Low-affinity binding sites for glycine-extended gastrin and amidated gastrin were present, but high-affinity binding sites were not detected with the appropriate iodinated ligands. In addition, neither glycine-extended gastrin nor amidated gastrin in the concentration range 10pmol/L-10nmol/L stimulated cell proliferation. We conclude that it is unlikely that the carcinoma cell lines LIM 1215, LIM 1839 and LIM 1899 use either amidated or glycine-extended gastrins as extracellular autocrine growth factors.
Kelly
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A
Department of Surgery, University of Melbourne, Victoria, Australia.
Hollande
F
F
Shulkes
A
A
Baldwin
G S
GS
D002460:Cell Line; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D011498:Protein Precursors / Q000378:metabolism; D011863:Radioimmunoassay; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism*
D005755:Gastrins; D006133:Growth Substances; D011498:Protein Precursors; D011949:Receptors, Cholecystokinin; C013706:big gastrin