Recombinant C-terminal fragments of the gastrin-releasing peptide precursor are bioactive.
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.
Patel
Oneel
O
University of Melbourne, Department of Surgery, Austin Health, Heidelberg, Melbourne, VIC, Australia.
Dumesny
Chelsea
C
Shulkes
Arthur
A
Baldwin
Graham S
GS
D000818:Animals; D041702:BALB 3T3 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D051379:Mice; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*; D011869:Radioligand Assay; D018004:Receptors, Bombesin / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D014162:Transfection
D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D018004:Receptors, Bombesin; D011994:Recombinant Proteins; C107120:bombesin receptor subtype 3; C047897:gastrin-releasing peptide precursor