Linked Life Data

11108243

Source:http://linkedlifedata.com/resource/pubmed/id/11108243

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2000-12-6
pubmed:abstractText
Metastasis of breast cancer to bone occurs with advanced disease and produces substantial morbidity. Secretion of PTH-related peptide (PTHrP) from breast cancer cells is thought to play a key role in osteolytic metastases and is increased by transforming growth factor-beta (TGFbeta), which is released from resorbed bone. Elevated extracellular calcium (Ca2+(o)) also stimulates PTHrP secretion from various normal and malignant cells, an action that could potentially be mediated by the Ca2+(o)-sensing receptor (CaR) originally cloned from the parathyroid gland. Indeed, we previously showed that both normal breast ductal epithelial cells and primary breast cancers express the CaR. In this study we investigated whether the MCF-7 and MDA-MB-231 human breast cancer cell lines express the CaR and whether CaR agonists modulate PTHrP secretion. Northern blot analysis and RT-PCR revealed bona fide CaR transcripts, and immunocytochemistry and Western analysis with a specific anti-CaR antiserum demonstrated CaR protein expression in both breast cancer cell lines. Furthermore, elevated Ca2+(o) and the polycationic CaR agonists, neomycin and spermine, stimulated PTHrP secretion dose dependently, with maximal, 2.1- to 2.3-fold stimulation. In addition, pretreatment of MDA-MB-231 cells overnight with TGFbeta1 (0.2, 1, or 5 ng/ml) augmented both basal and high Ca2+-stimulated PTHrP secretion. Thus, in PTHrP-secreting breast cancers metastatic to bone, the CaR could potentially participate in a vicious cycle in which PTHrP-induced bone resorption raises the levels of Ca2+(o) and TGFbeta within the bony microenvironment, which then act in concert to evoke further PTHrP release and worsening osteolysis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
141
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4357-64
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11108243-Blotting, Northern, pubmed-meshheading:11108243-Blotting, Western, pubmed-meshheading:11108243-Bone Neoplasms, pubmed-meshheading:11108243-Breast Neoplasms, pubmed-meshheading:11108243-Calcium, pubmed-meshheading:11108243-Humans, pubmed-meshheading:11108243-Immunohistochemistry, pubmed-meshheading:11108243-Neomycin, pubmed-meshheading:11108243-Parathyroid Hormone-Related Protein, pubmed-meshheading:11108243-Proteins, pubmed-meshheading:11108243-RNA, Messenger, pubmed-meshheading:11108243-Receptors, Calcium-Sensing, pubmed-meshheading:11108243-Receptors, Cell Surface, pubmed-meshheading:11108243-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11108243-Spermine, pubmed-meshheading:11108243-Transforming Growth Factor beta, pubmed-meshheading:11108243-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Extracellular calcium-sensing receptor expression and its potential role in regulating parathyroid hormone-related peptide secretion in human breast cancer cell lines.
pubmed:affiliation
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. jsanders@rics.bwh.harvard.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't