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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2007-2-7
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pubmed:abstractText |
Gastrin isoforms, acting through a variety of receptors, have proliferative and anti-apoptotic effects on gastrointestinal (GI) cancers. A small interfering RNA (siRNA) targeting the gastrin gene was used to investigate the role of endogenous gastrin in GI cancer cell survival. Downregulation of the gastrin gene in siRNA-transfected cells was measured using real-time reverse transcriptase-PCR. The most effective siRNA was tested in a panel of GI cancer cell lines at various concentrations and time points, and the effect on cell survival and apoptosis was measured using methyl thiazoyl tetrazolium (MTT) and caspase 3 activation assays. Gastrin siRNA reduced gene expression by more than 90% in a range of GI cancer cell lines. Downregulation of the gastrin gene was dose-dependent and effective over approximately 1 week in vitro. However, downregulation at the protein level was delayed by 3-4 days. Gastrin siRNA-transfected cells showed up to a 60% reduction in growth and up to a 50% increase in apoptosis compared with control siRNA-transfected cells. The effects were most marked in the cell line with the highest constitutive level of gastrin gene expression (human metastatic colon, C170HM2) and in epidermal growth factor (EGF)-treated cells as the gastrin promoter contains an EGF-response element, gERE. The ability of the siRNAs to reduce survival of these GI cell lines is further evidence of the importance of autocrine and/or intracrine gastrin loops in GI cancer, where expression of the gastrin gene and autonomous gastrin appears widespread.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17262081-10404512,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17262081-7822434,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17262081-9691917
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0007-0920
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
96
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
464-73
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:17262081-Apoptosis,
pubmed-meshheading:17262081-Cell Line, Tumor,
pubmed-meshheading:17262081-Cell Survival,
pubmed-meshheading:17262081-Down-Regulation,
pubmed-meshheading:17262081-Epidermal Growth Factor,
pubmed-meshheading:17262081-Gastrins,
pubmed-meshheading:17262081-Gastrointestinal Neoplasms,
pubmed-meshheading:17262081-Humans,
pubmed-meshheading:17262081-RNA, Small Interfering,
pubmed-meshheading:17262081-RNA Interference
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pubmed:year |
2007
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pubmed:articleTitle |
Use of interfering RNA to investigate the role of endogenous gastrin in the survival of gastrointestinal cancer cells.
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pubmed:affiliation |
Academic Unit of Cancer Studies, D Floor, West Block, Queen's Medical Centre, University Hospital, Nottingham NG7 2UH, UK. anna.grabowska@nottingham.ac.uk
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pubmed:publicationType |
Journal Article
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