Linked Life Data

16832342

Source:http://linkedlifedata.com/resource/pubmed/id/16832342

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-1-19
pubmed:abstractText
Recent studies have identified roles for C/EBPbeta in cellular survival and tumorigenesis, however, the mechanisms through which C/EBPbeta regulates these processes are not fully understood. Previously, we demonstrated that C/EBPbeta(-/-) mice are resistant to carcinogen-induced skin tumorigenesis and in response to topical carcinogen treatment display a 17-fold increase in keratinocyte apoptosis compared to wild-type mice. Here, we have investigated the mechanisms through which C/EBPbeta regulates apoptosis in response to carcinogenic stress. Analysis of carcinogen-treated C/EBPbeta(-/-) mouse skin revealed a striking increase in the number of p53 immunopositive keratinocytes in the epidermis of C/EBPbeta(-/-) mice compared to wild-type mice and this increase was temporally associated with a concomitant anomalous increase in apoptosis. The increased levels of p53 were functional as Mdm2, Bcl-2, C/EBPalpha and p21 were differentially regulated in the epidermis of carcinogen-treated C/EBPbeta(-/-) mice. The increase in p53 protein was not associated with an increase in p53 mRNA levels. To determine whether p53 is required for the increased apoptosis in C/EBPbeta(-/-) mice, C/EBPbeta/p53 compound knockout mice were generated. Carcinogen-treated C/EBPbeta/p53 compound knockout mice did not display increased apoptosis demonstrating p53 is required for the proapoptotic phenotype in C/EBPbeta(-/-) mice. Our results demonstrate that altered keratinocyte survival in C/EBPbeta(-/-) mice results from aberrant regulation of p53 protein and function and indicate C/EBPbeta has a role in the negative regulation of p53 protein levels in response to carcinogen-induced stress.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
360-7
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:16832342-9,10-Dimethyl-1,2-benzanthracene, pubmed-meshheading:16832342-Animals, pubmed-meshheading:16832342-Apoptosis, pubmed-meshheading:16832342-CCAAT-Enhancer-Binding Protein-beta, pubmed-meshheading:16832342-Carcinogens, pubmed-meshheading:16832342-Cell Survival, pubmed-meshheading:16832342-Epidermis, pubmed-meshheading:16832342-Female, pubmed-meshheading:16832342-Gene Expression Regulation, Neoplastic, pubmed-meshheading:16832342-Immunoenzyme Techniques, pubmed-meshheading:16832342-In Situ Nick-End Labeling, pubmed-meshheading:16832342-Keratinocytes, pubmed-meshheading:16832342-Male, pubmed-meshheading:16832342-Mice, pubmed-meshheading:16832342-Mice, Inbred C57BL, pubmed-meshheading:16832342-Mice, Knockout, pubmed-meshheading:16832342-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:16832342-Proto-Oncogene Proteins c-mdm2, pubmed-meshheading:16832342-Proto-Oncogene Proteins p21(ras), pubmed-meshheading:16832342-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16832342-Tumor Suppressor Protein p53
pubmed:year
2007
pubmed:articleTitle
Decreased survival of C/EBP beta-deficient keratinocytes is due to aberrant regulation of p53 levels and function.
pubmed:affiliation
Cell Signaling and Cancer Group, Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695-7633, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural