RGD Reference Report - Suppression of the hypoxia-inducible factor-1 response in cervical carcinoma xenografts by proteasome inhibitors. - 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 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
Advanced Search (OLGA)

Suppression of the hypoxia-inducible factor-1 response in cervical carcinoma xenografts by proteasome inhibitors.

Authors: Birle, DC  Hedley, DW 
Citation: Birle DC and Hedley DW, Cancer Res. 2007 Feb 15;67(4):1735-43.
RGD ID: 2293193
Pubmed: PMID:17308115   (View Abstract at PubMed)
DOI: DOI:10.1158/0008-5472.CAN-06-2722   (Journal Full-text)

Experimental data suggest therapeutic advantage from selective disruption of the hypoxia response. We recently found that the proteasome inhibitor bortezomib decreases tumor carbonic anhydrase IX (CAIX) expression in colon cancer patients and herein report a companion laboratory study to test if this effect was the result of hypoxia-inducible factor (HIF) inhibition. Human cervical (SiHa and Me180) and colon (RKO) carcinoma cell lines were treated with bortezomib or the structurally unrelated proteasome inhibitor MG132 in normoxic and hypoxic conditions in vitro. Two different in vivo experiments investigated bortezomib effects after single dose (2 mg/kg, 24 h) or longer exposure in severe combined immunodeficient mice bearing SiHa xenografts. Treatment with either drug produced accumulation of HIF-1alpha in vitro but strongly inhibited the production of CAIX and vascular endothelial growth factor (VEGF) under hypoxia. This correlated with more than 10-fold reduction in HIF-1 transcriptional activity under hypoxic conditions. A similar effect of bortezomib was seen in vivo, using the nitroimidazole probe EF5 to define regions of tumor hypoxia and a triple immunofluorescence technique to measure the spatial distributions of HIF-1alpha and CAIX. Plasma VEGF levels decreased by approximately 90% during treatment with bortezomib, indicating that this agent can potently inhibit the hypoxia response in tumors.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CA9HumanUterine Cervical Neoplasms treatmentIDA  RGD 
Car9RatUterine Cervical Neoplasms treatmentISOCA9 (Homo sapiens) RGD 
Car9MouseUterine Cervical Neoplasms treatmentISOCA9 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Car9  (carbonic anhydrase 9)

Genes (Mus musculus)
Car9  (carbonic anhydrase 9)

Genes (Homo sapiens)
CA9  (carbonic anhydrase 9)


Additional Information