title: 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.
authors.affiliation: Department of Medical Laboratory, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Long
authors.forename: Ke
authors.initials: K
authors.lastname: Dong
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Shuhui
authors.initials: S
authors.lastname: Yang
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.forename: Junxia
authors.initials: J
authors.lastname: Wei
authors.forename: Huizhong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D043924:Angiogenesis Modulating Agents / Q000378:metabolism*; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D043924:Angiogenesis Modulating Agents; D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins