Linked Life Data

21630219

Source:http://linkedlifedata.com/resource/pubmed/id/21630219

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-6-1
pubmed:abstractText
Osteopontin (OPN) is a secreted phospho-protein that confers on cancer cells a migratory phenotype. We have recently shown that nicotine, a risk factor in pancreatic ductal adenocarcinoma (PDA), induces an alpha7-nicotine acetylcholine receptor (?7-nAChR)-mediated increase of OPN in PDA cells. In this study, we tested nicotine's effect on the expression of OPN splice variants (OPNa, b, c) in PDA cells. We also analyzed the correlation between patients' smoking history with OPN and ?7-nAChR levels. RT-PCR and UV-light-illumination of ethidium-bromide staining were used to examine the mRNA expression in tissue and PDA cells treated with or without nicotine (3-300 nM). Localization of total OPN, OPNc and ?7-nAChR was analyzed by immunohistochemistry, and their mRNA tissue expression levels were correlated with the patients' smoking history. PDA cells expressed varying levels of OPNa, OPNb, and ?7-nAChR. Nicotine treatment selectively induced denovo expression of OPNc and increased ?7-nAChR expression levels. In PDA tissue, OPNc was found in 87% of lesions, of which 73% were smokers. OPNc and total OPN levels were correlated in the tissue from patients with invasive PDA. Nicotine receptor was expressed in the invasive and premalignant lesions without clear correlation with smoking history. We show here for the first time that ?7-nAChR is expressed in PDA cells and tissues and is regulated by nicotine in PDA cells. This, together with our previous findings that ?7-nAChR mediates the metastatic effects of nicotine in PDA, suggest that combined targeting of ?7-nAChR and OPNc could be a valid novel therapeutic strategy for invasive PDA, especially in the smoking population.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1699-5848
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
893-904
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Expression and regulation of nicotine receptor and osteopontin isoforms in human pancreatic ductal adenocarcinoma.
pubmed:affiliation
Department of Surgery, Jefferson Pancreatic, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural