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Calcium insensitivity of FA-6, a cell line derived from a pancreatic cancer associated with humoral hypercalcemia, is mediated by the significantly reduced expression of the Calcium Sensitive Receptor transduction component p38 MAPK

Morgan, R, Fairfax, B and Pandha, HS (2006) Calcium insensitivity of FA-6, a cell line derived from a pancreatic cancer associated with humoral hypercalcemia, is mediated by the significantly reduced expression of the Calcium Sensitive Receptor transduction component p38 MAPK MOLECULAR CANCER, 5. ? - ?. ISSN 1476-4598

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Abstract

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 nonhomeostatic 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.

Item Type: Article
Uncontrolled Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Oncology, ACTIVATED PROTEIN-KINASE, HORMONE-RELATED PROTEIN, EXTRACELLULAR CALCIUM, SENSING RECEPTOR, (CA-O(2+))-SENSING RECEPTOR, MALIGNANCY, PROLIFERATION, BONE
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Divisions: Faculty of Health and Medical Sciences > Microbial and Cellular Sciences
Depositing User: Melanie Hughes
Date Deposited: 05 Nov 2010 11:34
Last Modified: 23 Sep 2013 18:39
URI: http://epubs.surrey.ac.uk/id/eprint/2595

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