Linked Life Data

18310092

Source:http://linkedlifedata.com/resource/pubmed/id/18310092

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-9-3
pubmed:abstractText
Prostate Zn(2+) concentrations are among the highest in the body, and a marked decrease in the level of this ion is observed in prostate cancer. Extracellular Zn(2+) is known to regulate cell survival and proliferation in numerous tissues. In spite of this, a signaling role for extracellular Zn(2+) in prostate cancer has not been established. In the present study, we demonstrate that prostate metastatic cells are impermeable to Zn(2+), but extracellular Zn(2+) triggers a metabotropic Ca(2+) rise that is also apparent in the presence of citrate. Employing fluorescent imaging, we measured this activity in androgen-insensitive metastatic human cell lines, PC-3 and DU-145, and in mouse prostate tumor TRAMP-1 cells but not in androgen-sensitive LNCaP cells. The Ca(2+) response was inhibited by Galphaq and phospholipase C (PLC) inhibitors as well as by intracellular Ca(2+) store depletion, indicating that it is mediated by a Gq-coupled receptor that activates the inositol phosphate (IP(3)) pathway consistent with the previously identified zinc-sensing receptor (ZnR). Zn(2+)-dependent extracellular signal-regulated kinase and AKT activation, as well as enhanced Zn(2+)-dependent cell growth and survival, were observed in PC-3 cells that exhibit ZnR activity, but not in a ZnR activity-deficient PC-3 subline. Interestingly, application of Zn(2+)-citrate (Zn(2+)Cit), at physiological concentrations, was followed by a profound functional desensitization of extracellular Zn(2+)-dependent signaling and attenuation of Zn(2+)-dependent cell growth. Our results indicate that extracellular Zn(2+) and Zn(2+)Cit, by triggering or desensitizing ZnR activity, distinctly regulate prostate cancer cell growth. Thus, therapeutic strategies based either on Zn(2+) chelation or administration of Zn(2+)Cit may be effective in attenuating prostate tumor growth.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1460-2180
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1692-700
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18310092-Animals, pubmed-meshheading:18310092-Calcium, pubmed-meshheading:18310092-Calcium Signaling, pubmed-meshheading:18310092-Cell Proliferation, pubmed-meshheading:18310092-Cell Survival, pubmed-meshheading:18310092-Enzyme Activation, pubmed-meshheading:18310092-Fura-2, pubmed-meshheading:18310092-Humans, pubmed-meshheading:18310092-Immunoblotting, pubmed-meshheading:18310092-Male, pubmed-meshheading:18310092-Mice, pubmed-meshheading:18310092-Mitogen-Activated Protein Kinases, pubmed-meshheading:18310092-Phosphatidylinositol 3-Kinases, pubmed-meshheading:18310092-Phosphorylation, pubmed-meshheading:18310092-Prostatic Neoplasms, pubmed-meshheading:18310092-Receptors, Cell Surface, pubmed-meshheading:18310092-Signal Transduction, pubmed-meshheading:18310092-Tumor Cells, Cultured, pubmed-meshheading:18310092-Zinc Compounds
pubmed:year
2008
pubmed:articleTitle
Extracellular zinc and zinc-citrate, acting through a putative zinc-sensing receptor, regulate growth and survival of prostate cancer cells.
pubmed:affiliation
Department of Morphology, Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion University, PO Box 653, Beer Sheva 84105, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't