RESUMO
Epithelial ovarian cancer (EOC) is one of the most lethal gynecological cancers despite a relatively low incidence. Angiogenesis, one of the hallmarks of cancer, is essential for the pathogenesis of EOC, which is related to the induction of angiogenic factors. We found that ELF3 was highly expressed in EOCs under hypoxia and functioned as a transcription factor for IGF1. The ELF3-mediated increase in the secretion of IGF1 and VEGF promoted endothelial cell proliferation, migration, and EOC angiogenesis. Although this situation was much exaggerated under hypoxia, ELF3 silencing under hypoxia significantly attenuated angiogenic activity in endothelial cells by reducing the expression and secretion of IGF1 and VEGF. ELF3 silencing attenuated angiogenesis and tumorigenesis in ex vivo and xenograft mouse models. Consequently, ELF3 plays an important role in the induction of angiogenesis and tumorigenesis in EOC as a transcription factor of IGF1. A detailed understanding of the biological mechanism of ELF3 may both improve current antiangiogenic therapies and have anticancer effects for EOC.
Assuntos
Proteínas de Ligação a DNA , Neoplasias Ovarianas , Proteínas Proto-Oncogênicas c-ets , Fatores de Transcrição , Animais , Carcinogênese/genética , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Células Endoteliais/metabolismo , Feminino , Humanos , Hipóxia , Fator de Crescimento Insulin-Like I/genética , Camundongos , Neovascularização Patológica/patologia , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas c-ets/genética , Receptor IGF Tipo 1/genética , Fatores de Transcrição/genética , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: In acute infarction involving the anterior circulation, the ipsilateral posterior cerebral artery (PCA) often appears to be longer than the contralateral PCA on magnetic resonance angiography. We described this finding as dominant ipsilateral PCA (DIPCA). We sought to find the frequency of DIPCA and its predictors. METHODS: We recruited 164 consecutive individuals with acute infarct involving the anterior circulation, and analyzed their radiological and clinical features. RESULTS: DIPCA was noted in 27 patients (16.5%). It was more frequent in patients with than in patients without steno-occlusive disease of the ipsilateral anterior circulation (30.5 vs. 2.4%, p < 0.001). Multivariate analysis revealed a significant relationship between the severity of arterial lesions in the ipsilateral anterior circulation and DIPCA (p = 0.039). CONCLUSIONS: DIPCA may reflect increased leptomeningeal collateral flow via the ipsilateral PCA, and its development may be dependent on the stenotic anterior circulation.