Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2α and survival.
Hypoxia and its down-stream activated pathways are commonly involved in tumor progression. Genes involved in angiogenesis and glycolysis, i.e. vascular endothelial growth factor (VEGF) and lactase dehydrogenase A (LDHA), respectively, are transcriptionally controlled by the hypoxia inducible factors...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Journal article |
| Sprog: | English |
| Udgivet: |
2012
|
| _version_ | 1826271628143624192 |
|---|---|
| author | Giatromanolaki, A Sivridis, E Bechrakis, N Willerding, G St Charitoudis, G Foerster, M Gatter, K Harris, A Koukourakis, M |
| author_facet | Giatromanolaki, A Sivridis, E Bechrakis, N Willerding, G St Charitoudis, G Foerster, M Gatter, K Harris, A Koukourakis, M |
| author_sort | Giatromanolaki, A |
| collection | OXFORD |
| description | Hypoxia and its down-stream activated pathways are commonly involved in tumor progression. Genes involved in angiogenesis and glycolysis, i.e. vascular endothelial growth factor (VEGF) and lactase dehydrogenase A (LDHA), respectively, are transcriptionally controlled by the hypoxia inducible factors 1α and 2α (HIF1α and HIF2α). A series of 60 uveal melanomas were immunohistochemically assessed for the expression of VEGF and the phosphorylated/activated form of VEGF receptor 2 (pVEGFR2/KDR), after binding to VEGF. The expression of HIF1α, HIF2α and LDH5 was also investigated. Uveal melanomas overexpressing HIF2α (but not that of HIF1α) were significantly associated with high VEGF (P = 0.005), pVEGFR2/KDR (P < 0.0001) and LDH5 (P ≤ 0.0001). High LDH5 was linked with tumor necrosis (P = 0.01) and increased tumor size (P = 0.03). High VEGF was linked with phosphorylated pVEGFR2/KDR receptors. In univariate analysis high pVEGFR2/KDR receptor expression was significantly related with poor prognosis (P = 0.02). It is concluded that HIF2α plays an important role in the progression of uveal melanomas possibly by promoting the autocrine loop VEGF-pVEGFR2/KDR, and by enhancing the expression of LDHA gene, conferring thus a growth advantage. As pVEGFR2/KDR expression was significantly related with poor prognosis, inhibitors of this receptor may improve the clinical outcome of patients with pVEGFR2/KDR overexpressing uveal melanomas. |
| first_indexed | 2024-03-06T21:59:38Z |
| format | Journal article |
| id | oxford-uuid:4e22c3b2-8a0f-49f3-8bd2-18f70d6b9683 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:59:38Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:4e22c3b2-8a0f-49f3-8bd2-18f70d6b96832022-03-26T15:59:32ZPhosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2α and survival.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4e22c3b2-8a0f-49f3-8bd2-18f70d6b9683EnglishSymplectic Elements at Oxford2012Giatromanolaki, ASivridis, EBechrakis, NWillerding, GSt Charitoudis, GFoerster, MGatter, KHarris, AKoukourakis, MHypoxia and its down-stream activated pathways are commonly involved in tumor progression. Genes involved in angiogenesis and glycolysis, i.e. vascular endothelial growth factor (VEGF) and lactase dehydrogenase A (LDHA), respectively, are transcriptionally controlled by the hypoxia inducible factors 1α and 2α (HIF1α and HIF2α). A series of 60 uveal melanomas were immunohistochemically assessed for the expression of VEGF and the phosphorylated/activated form of VEGF receptor 2 (pVEGFR2/KDR), after binding to VEGF. The expression of HIF1α, HIF2α and LDH5 was also investigated. Uveal melanomas overexpressing HIF2α (but not that of HIF1α) were significantly associated with high VEGF (P = 0.005), pVEGFR2/KDR (P < 0.0001) and LDH5 (P ≤ 0.0001). High LDH5 was linked with tumor necrosis (P = 0.01) and increased tumor size (P = 0.03). High VEGF was linked with phosphorylated pVEGFR2/KDR receptors. In univariate analysis high pVEGFR2/KDR receptor expression was significantly related with poor prognosis (P = 0.02). It is concluded that HIF2α plays an important role in the progression of uveal melanomas possibly by promoting the autocrine loop VEGF-pVEGFR2/KDR, and by enhancing the expression of LDHA gene, conferring thus a growth advantage. As pVEGFR2/KDR expression was significantly related with poor prognosis, inhibitors of this receptor may improve the clinical outcome of patients with pVEGFR2/KDR overexpressing uveal melanomas. |
| spellingShingle | Giatromanolaki, A Sivridis, E Bechrakis, N Willerding, G St Charitoudis, G Foerster, M Gatter, K Harris, A Koukourakis, M Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2α and survival. |
| title | Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2α and survival. |
| title_full | Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2α and survival. |
| title_fullStr | Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2α and survival. |
| title_full_unstemmed | Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2α and survival. |
| title_short | Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2α and survival. |
| title_sort | phosphorylated pvegfr2 kdr receptor expression in uveal melanomas relation with hif2α and survival |
| work_keys_str_mv | AT giatromanolakia phosphorylatedpvegfr2kdrreceptorexpressioninuvealmelanomasrelationwithhif2aandsurvival AT sivridise phosphorylatedpvegfr2kdrreceptorexpressioninuvealmelanomasrelationwithhif2aandsurvival AT bechrakisn phosphorylatedpvegfr2kdrreceptorexpressioninuvealmelanomasrelationwithhif2aandsurvival AT willerdingg phosphorylatedpvegfr2kdrreceptorexpressioninuvealmelanomasrelationwithhif2aandsurvival AT stcharitoudisg phosphorylatedpvegfr2kdrreceptorexpressioninuvealmelanomasrelationwithhif2aandsurvival AT foersterm phosphorylatedpvegfr2kdrreceptorexpressioninuvealmelanomasrelationwithhif2aandsurvival AT gatterk phosphorylatedpvegfr2kdrreceptorexpressioninuvealmelanomasrelationwithhif2aandsurvival AT harrisa phosphorylatedpvegfr2kdrreceptorexpressioninuvealmelanomasrelationwithhif2aandsurvival AT koukourakism phosphorylatedpvegfr2kdrreceptorexpressioninuvealmelanomasrelationwithhif2aandsurvival |