Overexpression of astrocyte-elevated gene-1 is associated with cervical carcinoma progression and angiogenesis

Abstract

Astrocyte-elevated gene-1 (AEG-1) is implicated in the oncogenesis and angiogenesis of various types of human cancers. However, the biological roles of AEG-1 in cervical carcinoma remain to be further elucidated. In the present study, we demonstrated that the expression of AEG-1 was markedly upregulated in the cervical carcinoma cell lines HeLa, CaSki and SiHa, as well as in 8 paired primary cervical carcinoma tissue (CCT) specimens at both the transcriptional and translational levels when compared with normal cervical epithelial cells (NCECs). Furthermore, immunohistochemical (IHC) analysis demonstrated that 180 of 200 (90%) archived CCT specimens exhibited positive staining for AEG-1, and statistical analysis revealed that the upregulation of AEG-1 was significantly correlated with the clinical staging of the patients (P=0.034), including T (P=0.019), N (P=0.038) and M classification (P=0.018) as well as tumor differentiation (P=0.043). Furthermore, loss‑ and gain‑of‑function results showed that knockdown of AEG-1 expression by specific shRNA not only inhibited SiHa cell proliferation and invasive ability, but also significantly decreased the expression of the angiogenesis-related genes HIF-1α, Tie2, VEGF and TEM1/CD248. Moreover, an increased vascular formation ability was observed in human umbilical vein endothelial cells (HUVECs) co-cultured with conditioned medium both from SiHa cells and NCECs transfected with ectopic AEG-1. In conclusion, these results suggest that elevated expression of AEG-1 plays an important role in the aggressiveness and angiogenesis of cervical carcinoma and that AEG‑1 represents a novel and valuable predictive factor for the prognostic evaluation of cervical carcinoma patients.

Astrocyte Elevated Gene-1 Promotes Progression of Cervical Squamous Cell Carcinoma by Inducing Epithelial-Mesenchymal Transition via Wnt Signaling

“…6,9,10,18,19 In our study, AEG-1 overexpression was found to be significantly associated with lymph node metastasis, parametrial involvement, submucosa stromal invasion, and vascular invasion of CSCC. The results partly accorded with the studies of Huang et al 20 and Long et al 21 Huang et al 20 reported that a high level of AEG-1 correlated with lymphatic metastasis and tumor size of cervical cancer, but they did not present the correlation of AEG-1 with the parametrial involvement, stromal invasion, and vascular invasion of cervical cancer. Long et al 21 reported that AEG-1 was related to the clinical stage of cervical carcinoma.…”

“…It is reported that AEG-1 could promote the proliferation and angiogenesis of cervical carcinoma. 13,21 However, our data showed that AEG-1 was also implicated in the progression of cervical squamous carcinoma, at least in part, by promoting EMT. In addition, high level of AEG-1 was found to be related to unfavorable prognosis, meaning that AEG-1 may be a useful prognostic factor for CSCC.…”

EMT in cervical cancer: Its role in tumour progression and response to therapy

“…The overexpression of AEG-1 (in cervical carcinoma cells) significantly accelerates the invasive ability of cervical cancer cells [31]. This gene represents a novel and valuable predictive factor for the prognostic evaluation of cervical carcinoma [32]. The inhibition of AEG-1 by RNAi significantly decreases the invasion and migration of cervical cancer cells.…”

AEG‐1 induces gastric cancer metastasis by upregulation of eIF4E expression

“…AEG‐1/MTDH was subsequently found to mediate the metastasis of breast cancer 8. In recent years, AEG‐1 expression was found to be elevated and correlated with clinical tumour type, stage, metastasis and prognosis in a variety of cancers, including breast 9, lung 10, colorectal 11, cervical 12, 13, head and neck 14, hepatocellular 15 and gastric cancers 16, 17. AEG‐1 has been shown to be transcriptionally up‐regulated by Ha‐Ras‐activated PI3K and c‐Myc 18.…”