RGD Reference Report - Reduced ATM kinase activity and an attenuated p53 response to DNA damage in carcinogen-induced preneoplastic hepatic lesions in the rat. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Reduced ATM kinase activity and an attenuated p53 response to DNA damage in carcinogen-induced preneoplastic hepatic lesions in the rat.

Authors: Silins, I  Finnberg, N  Stahl, A  Hogberg, J  Stenius, U 
Citation: Silins I, etal., Carcinogenesis. 2001 Dec;22(12):2023-31.
RGD ID: 1599367
Pubmed: PMID:11751435   (View Abstract at PubMed)

In previous studies we have demonstrated that the p53 response to DNA damage in preneoplastic liver lesions, referred to as enzyme-altered foci (EAF), is attenuated. In the present investigation comparative quantitative RT-PCR revealed no major difference in the p53 mRNA levels in EAF and non-EAF tissue. When CoCl(2) was employed to induce hypoxia-inducible factor (HIF-1alpha), both non-EAF and EAF hepatocytes readily accumulated p53, whereas EAF hepatocytes did not accumulate p53 upon treatment with diethylnitrosamine (DEN). The p53 response was also induced in EAF hepatocytes by the inhibitor of nuclear export, leptomycin B. An inhibitor of DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutated (ATM), wortmannin, blocked the DEN-induced p53 response in non-EAF hepatocytes. Assay of kinase activity in immunoprecipitated material from EAF and non-EAF tissue revealed attenuated ATM activity in EAF. Immunohistological and western blot analysis of the level of ATM protein was in agreement with the activity measurements and no phosphorylation of Ser15 in p53 was detected in EAF tissue 24 h after a challenging dose of DEN. Taken together with previously published data, these data indicate selective attenuation of the DNA damage pathway in EAF hepatocytes. Down-regulation of DNA damage-induced and ATM-mediated phosphorylation of p53 may confer a growth advantage on EAF hepatocytes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pre-malignant neoplasm  ISOAtm (Rattus norvegicus)1599367protein:decreased expression:hepatocyteRGD 
pre-malignant neoplasm  ISOAtm (Rattus norvegicus)1599367 RGD 
pre-malignant neoplasm  IEP 1599367protein:decreased expression:hepatocyteRGD 

Objects Annotated

Genes (Rattus norvegicus)
Atm  (ATM serine/threonine kinase)

Genes (Mus musculus)
Atm  (ataxia telangiectasia mutated)

Genes (Homo sapiens)
ATM  (ATM serine/threonine kinase)


Additional Information