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Title: PPARalpha agonists stimulate progastrin production in human colorectal carcinoma cells.
Austin 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
Publication information: 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.
Gov't Doc #: 15177943
DOI: 10.1016/j.regpep.2004.03.015
Journal: Regulatory peptides
Type: Journal Article
Subjects: Bezafibrate.pharmacology
Cell Proliferation.drug effects
Clofibric Acid.analogs & derivatives.pharmacology
Colorectal Neoplasms.genetics.metabolism.pathology
Fibric Acids
Hypolipidemic Agents.pharmacology
Peroxisome Proliferator-Activated Receptors.agonists.antagonists & inhibitors.physiology
Protein Precursors.metabolism
RNA, Messenger.genetics
Vasodilator Agents.pharmacology
Appears in Collections:Journal articles

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