Linked Life Data

11280799

Source:http://linkedlifedata.com/resource/pubmed/id/11280799

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-3-30
pubmed:abstractText
PTHrP (parathyroid hormone-related protein) overexpression by prostate carcinoma cells has been implicated in tumor progression. Although the biological effects of PTHrP can be mediated by the G-protein-coupled PTH/PTHrP receptor, PTHrP also has intracrine actions mediated by a nuclear localization sequence at residues 87-107. We investigated the effect of PTHrP transfection and treatment on production by prostate carcinoma cells of IL (interleukin)-8, which can regulate prostate cancer growth by angiogenic activity and growth-promoting effects. Six prostate cancer cell lines exhibited constitutive expression of PTHrP and IL-8 that were significantly correlated (r = 0.93; P < 0.01). We transfected wild-type and mutant PTHrP into these cells. Wild-type PTHrP1-173 and PTHrP33-173 lacking the PTH/PTHrP receptor-binding domain induced a 3-fold stimulation of IL-8 production but not production of another angiogenic factor, vascular endothelial growth factor. Transfection of the COOH-terminal truncation mutant PTHrP1-87 induced a 5-fold simulation of IL-8 and a 3-fold increase in IL-8 mRNA. Cells transfected with PTHrP1-87 and 1-173 also showed increased cell proliferation. In contrast, exogenous PTHrP1-34 and 1-86 peptides did not significantly affect IL-8 production; moreover, PTHrP-neutralizing antibodies did not inhibit the production of IL-8 by transfected PTHrP. Additional transfection studies with progressively COOH-terminally truncated PTHrP1-87 defined a 23-amino acid sequence, PTHrP65-87, required for PTHrP1-87 to robustly stimulate IL-8 in prostate cancer cells. Confocal microscopy and immunoassay demonstrated PTHrP1-87 nuclear localization. Our results demonstrate that PTHrP acts to induce IL-8 production in prostate cancer cells via an intracrine pathway independent of its classical nuclear localization sequence. This novel pathway could mediate the effects of PTHrP on the progression of prostate cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2282-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11280799-Amino Acid Sequence, pubmed-meshheading:11280799-Cell Division, pubmed-meshheading:11280799-Cell Nucleus, pubmed-meshheading:11280799-Humans, pubmed-meshheading:11280799-Immunoassay, pubmed-meshheading:11280799-Interleukin-8, pubmed-meshheading:11280799-Male, pubmed-meshheading:11280799-Microscopy, Confocal, pubmed-meshheading:11280799-Molecular Sequence Data, pubmed-meshheading:11280799-Nuclear Localization Signals, pubmed-meshheading:11280799-Parathyroid Hormone-Related Protein, pubmed-meshheading:11280799-Peptide Fragments, pubmed-meshheading:11280799-Prostatic Neoplasms, pubmed-meshheading:11280799-Protein Biosynthesis, pubmed-meshheading:11280799-Proteins, pubmed-meshheading:11280799-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11280799-Transfection, pubmed-meshheading:11280799-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Parathyroid hormone-related protein induces interleukin 8 production by prostate cancer cells via a novel intracrine mechanism not mediated by its classical nuclear localization sequence.
pubmed:affiliation
The Department of Medicine, University of California, and the Veterans Affairs Medical Center, San Diego 92161, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.