Low Concentrations of Beta-carotene Stimulate the Proliferation of Human Pancreatic Duct Epithelial Cells in a PKA-dependent Manner

Cancer Genomics - Proteomics

MOURAD MAJIDI²  HUSSEIN A. N. AL-WADEI²  MING-SOUND TSAO¹  HILDEGARD M. SCHULLER² 

[1] ivision of Cellular and Molecular Biology, Department of Pathology, Ontario Cancer Institute/Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canadaivision of Cellular and Molecular Biology, Department of Pathology, Ontario Cancer Institute/Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canadaivision of Cellular and Molecular Biology, Department of Pathology, Ontario Cancer Institute/Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada;xperimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, U.S.A.xperimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, U.S.A.xperimental Oncology Laboratory, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, U.S.A.

关键词: Beta-carotene;    PKA;    cell proliferation;    pancreatic duct epithelia;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

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 μM). 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.

【 授权许可】

Unknown