RGD Reference Report - Renal carcinogenesis in models of diabetes in rats: metabolic changes are closely related to neoplastic development. - 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

Renal carcinogenesis in models of diabetes in rats: metabolic changes are closely related to neoplastic development.

Authors: Dombrowski, F  Klotz, L  Bannasch, P  Evert, M 
Citation: Dombrowski F, etal., Diabetologia. 2007 Dec;50(12):2580-90. Epub 2007 Oct 19.
RGD ID: 7242846
Pubmed: PMID:17952403   (View Abstract at PubMed)
DOI: DOI:10.1007/s00125-007-0838-2   (Journal Full-text)

AIMS/HYPOTHESIS: There is an increased risk of renal cell carcinoma (RCC) in human diabetes mellitus. We therefore examined the influence of hyperglycaemia and glucose-lowering treatment on nephrocarcinogenesis in rats. METHODS: Rats (n = 850), which were either spontaneously diabetic, streptozotocin-diabetic or normoglycaemic, were examined with special reference to Armanni-Ebstein lesions (AEL). RESULTS: Irrespective of the cause of diabetes, diabetic but not normoglycaemic rats developed typical glycogenotic clear-cell AEL. AEL showed strong proliferative activity, which was nearly completely inhibited by EGF receptor blockade (Gefitinib treatment). Many findings suggested a stepwise development of RCCs from AEL. Whereas the number and size of RCCs gradually increased in all diabetic groups, beginning at 6 months after onset of diabetes, normoglycaemic controls did not developed RCC. After 28 months, up to 82% of diabetic animals had at least one RCC. In contrast to the proximal tubules, the distal tubular system, including glycogenotic AEL, had the same levels of enzyme activities as RCC (e.g. high glycogen phosphorylase and synthase activity, lack of glucose 6-phosphatase activity) and the same expression patterns of cytokeratin 7 and several growth factors, along with their receptors and signal transduction proteins (TGF-alpha, EGF receptor, IGF-I, IGF-I receptor, IGF-II receptor, insulin receptor substrate 1, v-raf-1 murine leukemia viral oncogene homologue 1 and mitogen activated protein kinase kinase 1). In addition, direct morphological transitions between distal tubules, AEL and RCCs were frequently observed. All these findings indicate a common origin and a precursor-product relationship of AEL and RCCs. CONCLUSIONS/INTERPRETATION: Nephrocarcinogenesis in diabetic rats results from sustained hyperglycaemia, resulting in an adaptive metabolic response, altered growth factor signalling and subsequent neoplastic transformation of the tubular epithelial cells.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
renal cell carcinoma  ISOIgf1r (Rattus norvegicus)7242846; 7242846 RGD 
renal cell carcinoma  IEP 7242846 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Igf1r  (insulin-like growth factor 1 receptor)

Genes (Mus musculus)
Igf1r  (insulin-like growth factor I receptor)

Genes (Homo sapiens)
IGF1R  (insulin like growth factor 1 receptor)


Additional Information