Linked Life Data

14645111

Source:http://linkedlifedata.com/resource/pubmed/id/14645111

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-2-20
pubmed:abstractText
Using H-500 rat Leydig cancer cells as a model of humoral hypercalcemia of malignancy (HHM), we previously showed that high Ca(2+) induces PTH-related peptide (PTHrP) secretion via the calcium-sensing receptor (CaR) and mitogen- and stress-activated kinases, e.g. MAPK kinase 1 (MEK1), p38 MAPK, and stress-activated protein kinase 1/c-Jun N-terminal kinase. Because cellular proliferation is a hallmark of malignancy, we studied the role of the CaR in regulating the proliferation of H-500 cells. Elevated Ca(2+) has a mitogenic effect on these cells that is mediated by the CaR, because the calcimimetic NPS R-467 also induced proliferation. Inhibition of phosphatidylinositol 3-kinase (PI3K) and p38 MAPK but not MEK1 abolished the mitogenic effect. Activation of PI3K by elevated Ca(2+) was documented by phosphorylation of its downstream kinase, protein kinase B. Because protein kinase B activation promotes cell survival, we speculated that elevated Ca(2+) might protect H-500 cells against apoptosis. Using terminal uridine deoxynucleotidyl nick end labeling staining, we demonstrated that high Ca(2+) (7.5 mM) and NPS R-467 indeed protect cells against apoptosis induced by serum withdrawal compared with low Ca(2+) (0.5 mM). Because the CaR induces PTHrP secretion, it is possible that the mitogenic and antiapoptotic effects of elevated Ca(2+) could be indirect and mediated via PTHrP. However, blocking the type 1 PTH receptor with PTH (7-34) peptide did not alter either high Ca(2+)-induced proliferation or protection against apoptosis. Taken together, our data show that activation of PI3K and p38 MAPK but not of MEK1/ERK by the CaR promotes proliferation of H-500 cells as well as affords protection against apoptosis. These effects are likely direct without the involvement of PTHrP in an autocrine mode.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
145
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1211-7
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:14645111-Animals, pubmed-meshheading:14645111-Apoptosis, pubmed-meshheading:14645111-Calcium, pubmed-meshheading:14645111-Cell Division, pubmed-meshheading:14645111-Cell Line, Tumor, pubmed-meshheading:14645111-Humans, pubmed-meshheading:14645111-Hypercalcemia, pubmed-meshheading:14645111-Leydig Cell Tumor, pubmed-meshheading:14645111-MAP Kinase Kinase 1, pubmed-meshheading:14645111-MAP Kinase Signaling System, pubmed-meshheading:14645111-Male, pubmed-meshheading:14645111-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:14645111-Mitogen-Activated Protein Kinases, pubmed-meshheading:14645111-Neoplasm Transplantation, pubmed-meshheading:14645111-Parathyroid Hormone-Related Protein, pubmed-meshheading:14645111-Phosphatidylinositol 3-Kinases, pubmed-meshheading:14645111-Rats, pubmed-meshheading:14645111-Rats, Inbred F344, pubmed-meshheading:14645111-Receptors, Calcium-Sensing, pubmed-meshheading:14645111-Testicular Neoplasms, pubmed-meshheading:14645111-p38 Mitogen-Activated Protein Kinases
pubmed:year
2004
pubmed:articleTitle
Calcium-sensing receptor induces proliferation through p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase but not extracellularly regulated kinase in a model of humoral hypercalcemia of malignancy.
pubmed:affiliation
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine and Membrane Biology Program, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. jtfelt@rics.bwh.harvard.ed
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't