Linked Life Data

19073601

Source:http://linkedlifedata.com/resource/pubmed/id/19073601

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-2-9
pubmed:abstractText
Epidemiological studies have revealed that prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of cancer. Various mechanisms, including induction of apoptosis and inhibition of the growth and invasion of cancer cells, have been implicated in this anti-tumorigenic activity. In this study we focused on S100P, which is known to be overexpressed in clinically isolated tumors and which functions through both intracellular and extracellular mechanisms. We showed the up-regulation of S100P expression in human gastric carcinoma cells treated with various NSAIDs, including celecoxib. The celecoxib-mediated up-regulation of S100P was suppressed by the transfection of cells with small interfering RNA for activating transcription factor 4 (ATF4), a transcription factor involved in the endoplasmic reticulum stress response. Furthermore, deletion of ATF4 binding consensus sequence located in the promoter of the S100P gene resulted in inhibition of celecoxibmediated transcriptional activation of the gene. These results suggest that celecoxib up-regulates the expression of S100P through an ATF4-mediated endoplasmic reticulum stress response. Celecoxib inhibited the growth and induced apoptosis, and these actions could be either suppressed or stimulated by transfection of cells with S100P overexpression plasmid or small interfering RNA, respectively. Celecoxib also inhibited the invasive activity of the cells. Cromolyn, which inhibits the binding of S100P to its receptor, enhanced the celecoxib-mediated inhibition of cell invasion and growth but did not affect apoptosis. These results suggest that S100P affects apoptosis, cell growth, and invasion through either an intracellular or an extracellular mechanism and that the up-regulation of S100P expression by NSAIDs reduces their anti-tumorigenic activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4158-67
pubmed:meshHeading
pubmed-meshheading:19073601-Activating Transcription Factor 4, pubmed-meshheading:19073601-Animals, pubmed-meshheading:19073601-Anti-Asthmatic Agents, pubmed-meshheading:19073601-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:19073601-Apoptosis, pubmed-meshheading:19073601-Calcium-Binding Proteins, pubmed-meshheading:19073601-Cell Line, Tumor, pubmed-meshheading:19073601-Consensus Sequence, pubmed-meshheading:19073601-Cromolyn Sodium, pubmed-meshheading:19073601-Endoplasmic Reticulum, pubmed-meshheading:19073601-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19073601-Humans, pubmed-meshheading:19073601-Mice, pubmed-meshheading:19073601-Mice, Inbred NOD, pubmed-meshheading:19073601-Mice, SCID, pubmed-meshheading:19073601-Neoplasm Invasiveness, pubmed-meshheading:19073601-Neoplasm Proteins, pubmed-meshheading:19073601-Pyrazoles, pubmed-meshheading:19073601-Response Elements, pubmed-meshheading:19073601-Stomach Neoplasms, pubmed-meshheading:19073601-Sulfonamides, pubmed-meshheading:19073601-Up-Regulation
pubmed:year
2009
pubmed:articleTitle
Up-regulation of S100P expression by non-steroidal anti-inflammatory drugs and its role in anti-tumorigenic effects.
pubmed:affiliation
Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't