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The Calcium-Sensing Receptor is a key component of Calcium/Parathyroid hormone homeostatic system that helps maintain appropriate plasma Ca2+ concentrations. It also has a number of non-homeostatic functions, including cell cycle regulation through the p38 MAPK pathway, and recent studies have indicated that it is required for Ca2+ mediated growth arrest in pancreatic carcinoma cells. Some pancreatic cancers produce pathogenic amounts of parathyroid like hormones, however, which significantly increase Ca2+ plasma concentrations and might be expected to block further cell growth. In this study we have investigated the expression and function of the p38 MAPK signaling pathway in Ca2+ sensitive (T3M-4) and insensitive (FA6) pancreatic cancer cell lines. FA-6 cells, which are derived from a pancreatic adenocarcinoma that secretes a parathyroid hormone related peptide, exhibit only very low levels of p38 MAPK expression, relative to T3M-4 cells. Transfecting FA-6 cells with a p38 MAPK expression construct greatly increases their sensitivity to Ca2+. Furthermore, the reduction of p38 MAPK in T3M-4 cells significantly reduces the extent to which high levels of Ca2+ inhibit proliferation. These results suggest that the low levels of p38 MAPK expression in FA-6 cells may serve to reduce their sensitivity to high concentrations of external Ca2+ that would otherwise block proliferation.

Original publication

DOI

10.1186/1476-4598-5-51

Type

Journal

Molecular cancer

Publication Date

11/2006

Volume

5

Addresses

Postgraduate Medical School, University of Surrey, UK. r.morgan@surrey.ac.uk

Keywords

Cell Line, Tumor, Humans, Adenocarcinoma, Pancreatic Neoplasms, Hypercalcemia, Calcium, Parathyroid Hormone-Related Protein, p38 Mitogen-Activated Protein Kinases, Receptors, Calcium-Sensing, RNA, Messenger, Transfection, Cell Proliferation, Down-Regulation, RNA Interference