Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/10006
Title: Synthesis, expression and biological activity of the prohormone for gastrin releasing peptide (ProGRP).
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
Citation: 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.
Internal ID Number: 16223866
URI: http://ahro.austin.org.au/austinjspui/handle/1/10006
DOI: 10.1210/en.2005-0574
URL: http://www.ncbi.nlm.nih.gov/pubmed/16223866
Type: Journal Article
Subjects: Amino Acid Sequence
Animals
Cell Line, Tumor
Cloning, Molecular
Female
Gene Expression Regulation
Humans
Male
Mass Spectrometry
Molecular Sequence Data
Peptide Fragments.chemistry.genetics.metabolism
Peptides.chemistry.genetics.metabolism
Recombinant Fusion Proteins.metabolism
Recombinant Proteins.chemistry.genetics.metabolism
Appears in Collections:Journal articles

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