title: Parathyroid hormone and the regulation of cell cycle in colon adenocarcinoma cells.
abstract: Parathyroid hormone (PTH) functions as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. In this study, we investigated the role of PTH in the regulation of the cell cycle in human colon adenocarcinoma Caco-2 cells. Flow cytometry analysis revealed that PTH (10(-8)M, 12-24h) treatment increases the number of cells in the G0/G1 phase and diminishes the number in both phases S and G2/M. In addition, analysis by Western blot showed that the hormone increases the expression of the inhibitory protein p27Kip1 and diminishes the expression of cyclin D1, cyclin D3 and CDK6. However, the amounts of CDK4, p21Cip1, p15INK4B and p16INK4A were not different in the absence or presence of PTH. Inhibitors of PKC (Ro-318220, bisindolylmaleimide and chelerythine), but not JNK (SP600125) and PP2A (okadaic acid and calyculin A), reversed PTH response in Caco-2 cells. Taken together, our results suggest that PTH induces G0/G1 phase arrest of Caco-2 intestinal cells and changes the expression of proteins involved in cell cycle regulation via the PKC signaling pathway.
authors.affiliation: Dept. Biologia, Universidad Nacional del Sur, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Calvo
authors.forename: Claudia
authors.initials: C
authors.lastname: Gentili
authors.forename: Ana Russo
authors.initials: AR
authors.lastname: de Boland
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000873:Anthracenes / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D053119:Benzophenanthridines / Q000494:pharmacology; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology* / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D007211:Indoles; D010281:Parathyroid Hormone; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; C016299:chelerythrine; D011493:Protein Kinase C; D018844:Cyclin-Dependent Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C064758:Ro 31-8220