Low concentrations of beta-carotene stimulate the proliferation of human pancreatic duct epithelial cells in a PKA-dependent manner.
Journal - Cancer genomics & proteomics (Greece )
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is among the most common causes of cancer death. Preclinical and clinical studies on the preventive effects of beta-carotene or other retinoids have used dietary supplements that yielded high systemic concentrations (1-50 microM). While some of the preclinical data suggested cancer preventive effects of these agents, they have disappointed in clinical investigations. MATERIALS AND METHODS: The effects of low concentrations (10 fM-200 nM)of beta-carotene on the proliferation, intracellular cAMP levels, PKA activation status and phosphorylation of EGFR-specific tyrosine kinases and ERK1/2 in immortalized human pancreatic duct epithelial cells was investigated. RESULTS: Our data show significant concentration-dependent and PKA-dependent stimulation of all measured endpoints. Similar responses were achieved with forskolin. Our data indicate that low concentrations of beta-carotene stimulate the proliferation of the putative origin of PDAC, pancreatic duct epithelial cells via cAMP and PKA-dependent transactivation of the EGFR pathway. This could potentially have promoting effects on the development of PDAC.
|ISSN : ||1109-6535|
|Mesh Heading : ||Cell Proliferation Cell Survival Cells, Cultured Cyclic AMP-Dependent Protein Kinases Enzyme Activation Enzyme Induction Epithelial Cells Forskolin Humans Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Pancreatic Ducts Phosphorylation Receptor, Epidermal Growth Factor beta Carotene drug effects drug effects drug effects drug effects pharmacology biosynthesis biosynthesis enzymology drug effects metabolism|
|Mesh Heading Relevant : ||metabolism drug effects enzymology cytology drug effects pharmacology|