Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9747
Title: PPARalpha agonists stimulate progastrin production in human colorectal carcinoma cells.
Authors: Lachal, Shamilah;Ford, Joanne;Shulkes, Arthur;Baldwin, Graham S
Affiliation: Department of Surgery ARMC, University of Melbourne, Department of Surgery, Austin Health, Heidelberg, Victoria 3084, Australia.
Issue Date: 15-Aug-2004
Citation: Regulatory Peptides; 120(1-3): 243-51
Abstract: The three subtypes of peroxisome proliferator activated-receptors (PPARalpha, delta and gamma) control the storage and metabolism of fatty acids. Treatment of rats with the PPARalpha ligand ciprofibrate increases serum gastrin concentrations, and several lines of evidence suggest that non-amidated gastrins act as growth factors for the colonic mucosa. The aim of the present study was to investigate the expression of PPARs and the effect of PPAR ligands on gastrin production and cell proliferation in human colorectal carcinoma (CRC) cell lines. mRNAs for all three PPAR subtypes were detected by PCR in all CRC cell lines tested. The concentrations of progastrin, but not of glycine-extended or amidated gastrin, measured by radioimmunoassay in LIM 1899 conditioned media and cell extracts were significantly increased by treatment with the PPARalpha ligand clofibrate. Similar increases in progastrin were seen following treatment with the PPARalpha ligands ciprofibrate and fenofibrate, but not with bezafibrate, gemfibrozil or Wy 14643. The PPARgamma agonist rosiglitazone had no significant effect on progastrin production. The PPARalpha ligand clofibrate also stimulated proliferation of the LIM 1899 cell line. We conclude that some PPARalpha ligands increase progastrin production by the human CRC cell line LIM 1899, and that clofibrate increases proliferation of LIM 1899 cells. These studies have revealed a relationship between PPARs and gastrin, two regulatory molecules implicated in the pathogenesis of CRC.
Internal ID Number: 15177943
URI: http://ahro.austin.org.au/austinjspui/handle/1/9747
DOI: 10.1016/j.regpep.2004.03.015
URL: http://www.ncbi.nlm.nih.gov/pubmed/15177943
Type: Journal Article
Subjects: Bezafibrate.pharmacology
Cell Proliferation.drug effects
Clofibrate.pharmacology
Clofibric Acid.analogs & derivatives.pharmacology
Colorectal Neoplasms.genetics.metabolism.pathology
Fenofibrate.pharmacology
Fibric Acids
Gastrins.metabolism
Gemfibrozil.pharmacology
Humans
Hypolipidemic Agents.pharmacology
Ligands
Peroxisome Proliferator-Activated Receptors.agonists.antagonists & inhibitors.physiology
Protein Precursors.metabolism
Pyrimidines.pharmacology
RNA, Messenger.genetics
Radioimmunoassay
Thiazolidinediones.pharmacology
Vasodilator Agents.pharmacology
Appears in Collections:Journal articles

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