RGD Reference Report - Phosphorylated KDR expression in endometrial cancer cells relates to HIF1alpha/VEGF pathway and unfavourable prognosis. - Rat Genome Database

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Phosphorylated KDR expression in endometrial cancer cells relates to HIF1alpha/VEGF pathway and unfavourable prognosis.

Authors: Giatromanolaki, A  Koukourakis, MI  Turley, H  Sivridis, E  Harris, AL  Gatter, KC  Gatter, Kevin C 
Citation: Giatromanolaki A, etal., Mod Pathol. 2006 May;19(5):701-7.
RGD ID: 2291929
Pubmed: PMID:16557278   (View Abstract at PubMed)
DOI: DOI:10.1038/modpathol.3800579   (Journal Full-text)

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor for many malignant neoplasms exerting its function through activation of specific membrane receptors, that is, KDR/flk-1, residing in endothelial cells. Several recent reports indicate that VEGF receptors are also expressed in cancer cells, suggesting that specific VEGF-originated cancer cell reactions may parallel the endothelial response. Using a novel monoclonal antibody, recognizing the activated (phosphorylated) form of the KDR receptor (pKDR), we assessed the expression of pKDR in normal and malignant endometrium. A strong and consistent cytoplasmic and nuclear pKDR expression was noted in the normally cycling endometrium, including epithelial, stromal and endothelial cells, suggesting a role in the normal menstrual cycle. Approximately, one-third of the 70 stage I endometrioid adenocarcinomas analysed exhibited an intense cytoplasmic and nuclear pKDR expression in both cancer cells and peritumoral vessels. It was noted that such pKDR reactivity in cancer cells was related directly to VEGF, VEGF/KDR complexes and HIF1alpha (hypoxia inducible factor 1alpha) expression. Furthermore, pKDR expression was significantly associated with poor prognosis. It is concluded that the VEGF/KDR pathway is activated in both normally cycling and malignant endometrium, suggestive of an important role in the biology of this tissue. The unfavourable prognosis that VEGF confers to endometrial adenocarcinomas could be attributed to its angiogenic activity, but also to a direct effect on cancer cells through an autocrine VEGF/KDR loop.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KDRHumanEndometrioid Carcinomas severityIEP protein:increased expression and increased phosphorylation:tumor:pKDR expression associated with poor overall survival (P=0.009)RGD 
KdrRatEndometrioid Carcinomas severityISOKDR (Homo sapiens) RGD 
KdrMouseEndometrioid Carcinomas severityISOKDR (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kdr  (kinase insert domain receptor)

Genes (Mus musculus)
Kdr  (kinase insert domain protein receptor)

Genes (Homo sapiens)
KDR  (kinase insert domain receptor)


Additional Information