Linked Life Data

10698490

Source:http://linkedlifedata.com/resource/pubmed/id/10698490

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-3-16
pubmed:abstractText
The tumor suppressor gene p53 is a potent transcriptional regulator of genes which are involved in many cellular activities including cell cycle arrest, apoptosis, and angiogenesis. Recent studies have demonstrated that the activation of the transcriptional factor nuclear factor kappaB (NF-kappaB) plays an essential role in preventing apoptotic cell death. In this study, to better understand the mechanism responsible for the p53-mediated apoptosis, the effect of wild-type p53 (wt-p53) gene transfer on nuclear expression of NF-kappaB was determined in human colon cancer cell lines. A Western blot analysis of nuclear extracts demonstrated that NF-kappaB protein levels in the nuclei were suppressed by the transient expression of the wt-p53 in a dose-dependent manner. Transduced wt-p53 expression increased the cytoplasmic expression of I kappaB alpha as well as its binding ability to NF-kappaB, thus markedly reducing the amount of NF-kappaB that translocated to the nucleus. The decrease in nuclear NF-kappaB protein correlated with the decreased NF-kappaB constitutive activity measured by electrophoretic mobility shift assay. Furthermore, parental cells transfected with NF-kappaB were better protected from cell death induced by the wt-p53 gene transfer. We also found that the wt-p53 gene transfer was synergistic with aspirin (acetylsalicylic acid) in inhibiting NF-kappaB constitutive activity, resulting in enhanced apoptotic cell death. These results suggest that the inhibition of NF-kappaB activity is a plausible mechanism for apoptosis induced by the wt-p53 gene transfer in human colon cancer cells and that anti-NF-kappaB reagent aspirin could make these cells more susceptible to apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
726-36
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10698490-Adenocarcinoma, pubmed-meshheading:10698490-Adenoviruses, Human, pubmed-meshheading:10698490-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:10698490-Apoptosis, pubmed-meshheading:10698490-Aspirin, pubmed-meshheading:10698490-Cell Nucleus, pubmed-meshheading:10698490-Colonic Neoplasms, pubmed-meshheading:10698490-Cytomegalovirus, pubmed-meshheading:10698490-DNA-Binding Proteins, pubmed-meshheading:10698490-Gene Expression Regulation, pubmed-meshheading:10698490-Genes, p53, pubmed-meshheading:10698490-Genetic Vectors, pubmed-meshheading:10698490-Humans, pubmed-meshheading:10698490-I-kappa B Proteins, pubmed-meshheading:10698490-NF-kappa B, pubmed-meshheading:10698490-Neoplasm Proteins, pubmed-meshheading:10698490-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10698490-Transcription, Genetic, pubmed-meshheading:10698490-Tumor Cells, Cultured, pubmed-meshheading:10698490-Tumor Suppressor Protein p53
pubmed:year
2000
pubmed:articleTitle
Overexpression of the wild-type p53 gene inhibits NF-kappaB activity and synergizes with aspirin to induce apoptosis in human colon cancer cells.
pubmed:affiliation
First Department of Surgery, Okayama University Medical School, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't