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Title: Synthesis, expression and biological activity of the prohormone for gastrin releasing peptide (ProGRP).
Austin Authors: Dumesny, Chelsea;Patel, Oneel;Lachal, Shamilah;Giraud, Andrew S;Baldwin, Graham S;Shulkes, Arthur
Affiliation: Department of Surgery, Austin Health, University of Melbourne, Heidelberg, Victoria 3084, Australia
Issue Date: 13-Oct-2005
Publication information: Endocrinology 2005; 147(1): 502-9
Abstract: Gastrin-releasing peptide (GRP) has a widespread distribution and multiple stimulating effects on endocrine and exocrine secretions and metabolism. The prohormone for GRP (ProGRP, 125 amino acids) is processed to the amidated, biologically active end products GRP(1-27) and GRP(18-27). Amidated forms of GRP are putative autocrine or paracrine growth factors in a number of cancers including colorectal cancer. However, the potential role and biological activity of proGRP has not been investigated. Using a newly developed antisera directed to the N terminus of human proGRP, proGRP immunoreactivity was detected in all of the endometrial, prostate, and colon cancer cell lines tested and in nine of 10 resected colorectal carcinomas. However, no amidated forms were detected, suggesting an attenuation of processing in tumors. Recombinant proGRP was expressed as a His-tag fusion protein and purified by metal affinity chromatography and HPLC. ProGRP stimulated proliferation of a colon cancer cell line and activated MAPK, but unlike GRP(18-27)amide had no effect on inositol phosphate production. ProGRP did not compete with iodinated bombesin in binding assays on Balb-3T3 cells transfected with the known GRP receptors, GRP-R or BRS-3. We conclude that proGRP is present in a number of cancer cell lines and in resected colorectal tumors and is biologically active. Our results suggest that antagonists to GRP precursors rather than the amidated end products should be developed as a treatment for colorectal and other cancers that express proGRP-derived peptides.
Gov't Doc #: 16223866
DOI: 10.1210/en.2005-0574
Journal: Endocrinology
Type: Journal Article
Subjects: Amino Acid Sequence
Cell Line, Tumor
Cloning, Molecular
Gene Expression Regulation
Mass Spectrometry
Molecular Sequence Data
Peptide Fragments.chemistry.genetics.metabolism
Recombinant Fusion Proteins.metabolism
Recombinant Proteins.chemistry.genetics.metabolism
Appears in Collections:Journal articles

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