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C-terminal fragments from the precursor for gastrin-releasing peptide (GRP) have been detected in several human tumour types. We have previously demonstrated that recombinant human proGRP42-98 is biologically active. To investigate the regions responsible, proGRP42-98 was cleaved with thrombin, and the fragments purified by HPLC. Both proGRP42-79 and proGRP80-98 stimulated proliferation of the human colorectal carcinoma cell line DLD-1, but neither peptide bound to the GRP receptor or bombesin receptor subtype 3. We conclude that two distinct regions of the proGRP C-terminus are biologically active, via a receptor distinct from the known GRP receptors. This discovery opens the way for the development of selective antagonists that may offer new therapies for proGRP-producing tumours. |
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