AEG-1 Contributes to Metastasis in Hypoxia-Related Ovarian Cancer by Modulating the HIF-1alpha/NF-kappaB/VEGF Pathway

作者：Yu, Xiaoyu; Wang, Yan; Qiu, Huilei; Song, Hongtao; Feng, Di; Jiang, Yang; Deng, Shuzhe; Meng, Hongxue; Geng, Jingshu^*

来源：Biomed Research International, 2018, 2018: 3145689.

DOI：10.1155/2018/3145689

• ASTROCYTE ELEVATED GENE-1
• BREAST-CANCER
• INDUCIBLE FACTOR-1
• EXPRESSION
• ASTROCYTE-ELEVATED-GENE-1
• PROGRESSION
• ACTIVATION
• CARCINOMA
• CLONING

Objective. Ovarian carcinoma represents one of the deadliest malignancies among female cancer patients. Astrocyte-elevated gene-1 (AEG-1) participates in the ontogenesis of multiple human malignant diseases. Here we evaluated AEG-1, hypoxia-inducible factor- (HIF-) 1 alpha, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B), and vascular endothelial growth factor (VEGF) amounts in hypoxia induced ovarian carcinoma cells. This study aimed to explore the mechanism by which AEG-1 regulates metastasis in hypoxia induced ovarian carcinoma. Patients and Methods. AEG-1, HIF-1 alpha, and VEGF protein amounts were evaluated by immunohistochemistry in 40 and 170 normal ovary and ovarian cancer tissue specimens, respectively. In addition, AEG-1, HIF-1 alpha NF-kappa B, and VEGF mRNA and protein levels were determined by reverse quantified RT-PCR and WB, respectively, at different time periods (0-24 h) in epithelial ovarian cancer (EOC) SKOV3 cells treated in a hypoxia incubator. Furthermore, NF-kappa B and VEGF gene and protein expression levels in AEG-1 knockdown EOC cells were quantitated by RT-PCR and WB, respectively. Results. AEG-1, HIF-1 alpha, and VEGF amounts were significantly elevated in EOC tissue samples compared with normal ovary specimens (p < 0.001). Positive expression of HIF-1 alpha and AEG-1 was associated with higher metastatic rate (p < 0.01), lower FIGO stage (p < 0.001), and degree of differentiation (p < 0.001). Meanwhile, EOC SKOV3 cells grew upon exposure to hypoxia for 8 h (p < 0.001); at this time point, AEG-1, HIF-1 alpha, NF-kappa B, and VEGF amounts peaked (p < 0.001), at both the gene and the protein levels. After AEG-1 knockdown, HIF-1 alpha, NF-kappa B, and VEGF amounts were significantly decreased in EOC SKOV3 cells, also under hypoxic conditions (p < 0.01). Conclusions. As an independent prognostic factor, AEG-1 was found to be significantly associated with hypoxia in ovarian cancer by regulating the HIF-1alpha/NF-kappaB/VEGF pathway. Therefore, AEG-1 may be useful in determining disease stage and prognosis in ovarian cancer.

• 出版日期2018
• 单位哈尔滨医科大学