Aspirin and alterations in DNA repair proteins in the SW480 colorectal cancer cell line.

2.50
Hdl Handle:
http://hdl.handle.net/2436/117148
Title:
Aspirin and alterations in DNA repair proteins in the SW480 colorectal cancer cell line.
Authors:
Dibra, H. K.; Brown, J. E.; Hooley, Paul; Nicholl, I. D.
Abstract:
Regular aspirin intake is associated with a reduction in the incidence of colorectal cancer. Aspirin has been shown to be cytotoxic to colorectal cancer cells in vitro. The molecular basis for this cytotoxicity is controversial, with a number of competing hypotheses in circulation. One suggestion is that the protective effect is related to the induction of expression of the DNA mismatch repair (MMR) proteins hMLH1, hMSH2, hMSH6 and hPMS2 in DNA MMR proficient cells. We report that treatment of the DNA MMR competent/p53 mutant colorectal cancer cell line SW480 with 1 mM aspirin for 48 h caused changes in mRNA expression of several key genes involved in DNA damage signalling pathways, including a significant down-regulation in transcription of the genes ATR, BRCA1 and MAPK12. Increases in the transcription of XRCC3 and GADD45alpha genes are also reported. Regulation of these genes could potentially have profound effects on colorectal cancer cells and may play a role in the observed chemo-protective effect of aspirin in vivo. Although a correlation was not seen between transcript and protein levels of ATR, BRCA1 and GADD45alpha, an increase in XRCC3 encoded protein expression upon aspirin treatment in SW480 cells was observed by immunoblotting, immunofluorescence and immunohistochemical analysis. This is the first report of XRCC3 gene transcription and encoded protein expression being susceptible to exposure to the non-steroidal anti-inflammatory drug, aspirin. Furthermore, this study indicates that alterations in gene transcription seen in microarray studies must be verified at the protein level.
Citation:
Oncology reports, 24 (1):37-46
Publisher:
Spandios Publications
Journal:
Oncology reports
Issue Date:
2010
URI:
http://hdl.handle.net/2436/117148
DOI:
10.3892/or_00000826
PubMed ID:
20514442
Type:
Article
Language:
en
ISSN:
1791-2431
Appears in Collections:
Applied Microbiology Research Group; Cancer Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorDibra, H. K.en
dc.contributor.authorBrown, J. E.en
dc.contributor.authorHooley, Paulen
dc.contributor.authorNicholl, I. D.en
dc.date.accessioned2010-12-03T16:04:31Z-
dc.date.available2010-12-03T16:04:31Z-
dc.date.issued2010-
dc.identifier.citationOncology reports, 24 (1):37-46en
dc.identifier.issn1791-2431-
dc.identifier.pmid20514442-
dc.identifier.doi10.3892/or_00000826-
dc.identifier.urihttp://hdl.handle.net/2436/117148-
dc.description.abstractRegular aspirin intake is associated with a reduction in the incidence of colorectal cancer. Aspirin has been shown to be cytotoxic to colorectal cancer cells in vitro. The molecular basis for this cytotoxicity is controversial, with a number of competing hypotheses in circulation. One suggestion is that the protective effect is related to the induction of expression of the DNA mismatch repair (MMR) proteins hMLH1, hMSH2, hMSH6 and hPMS2 in DNA MMR proficient cells. We report that treatment of the DNA MMR competent/p53 mutant colorectal cancer cell line SW480 with 1 mM aspirin for 48 h caused changes in mRNA expression of several key genes involved in DNA damage signalling pathways, including a significant down-regulation in transcription of the genes ATR, BRCA1 and MAPK12. Increases in the transcription of XRCC3 and GADD45alpha genes are also reported. Regulation of these genes could potentially have profound effects on colorectal cancer cells and may play a role in the observed chemo-protective effect of aspirin in vivo. Although a correlation was not seen between transcript and protein levels of ATR, BRCA1 and GADD45alpha, an increase in XRCC3 encoded protein expression upon aspirin treatment in SW480 cells was observed by immunoblotting, immunofluorescence and immunohistochemical analysis. This is the first report of XRCC3 gene transcription and encoded protein expression being susceptible to exposure to the non-steroidal anti-inflammatory drug, aspirin. Furthermore, this study indicates that alterations in gene transcription seen in microarray studies must be verified at the protein level.en
dc.language.isoenen
dc.publisherSpandios Publicationsen
dc.subject.meshAnti-Inflammatory Agents, Non-Steroidalen
dc.subject.meshAspirinen
dc.subject.meshCarcinomaen
dc.subject.meshCell Line, Tumoren
dc.subject.meshCell Survivalen
dc.subject.meshColorectal Neoplasmsen
dc.subject.meshDNA Repairen
dc.subject.meshDose-Response Relationship, Drugen
dc.subject.meshGene Expression Profilingen
dc.subject.meshGene Expression Regulation, Neoplasticen
dc.subject.meshHumansen
dc.subject.meshNeoplasm Proteinsen
dc.subject.meshOligonucleotide Array Sequence Analysisen
dc.titleAspirin and alterations in DNA repair proteins in the SW480 colorectal cancer cell line.en
dc.typeArticleen
dc.identifier.journalOncology reportsen

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