title: Epidermal growth factor (EGF) triggers the malignancy of hemangioma cells via activation of NF-κB signals.
abstract: Hemangioma (HA) is tumor formed by hyper-proliferation of vascular endothelial cells. However, the role and mechanisms of epidermal growth factor (EGF) on the progression of HA are not well illustrated. Our present study revealed that EGF can significantly promote the in vitro proliferation and motility of HA cells, which was confirmed by the up regulation of Bcl-2, proliferating cell nuclear antigen (PCNA), and metalloproteinase-2 (MMP-2) and MMP-9. The pharmacological inhibition of NF-κB, while not ERK1/2 or PI3K/Akt, attenuated EGF induced cell proliferation and expression of MMP-2 and MMP-9. EGF treatment also increased the phosphorylation, nuclear translocation and transcriptional activities of NF-κB in HA cells. These data suggested that NF-κB plays an essential role in EGF induced malignancy of HA cells. Furthermore, EGF treatment also increased the phosphorylation of IκB and IKKα, while not IKKβ or IKKγ. The knockdown of IKKα reversed EGF induced activation of NF-κB. EGF treatment also decreased the phosphorylation of GSK-3β and increased its activities in both HDEC and CRL-2586 EOMA cells. LiCl, a potent GSK-3β inhibitor, can obviously reverse EGF induced up regulation of p65 phosphorylation. Collectively, our study revealed that EGF can trigger the malignancy of HA cells via induction of proliferation and invasion. The activation of NF-κB through IKKα/IκBα and GSK-3β signal is essential for this process. It suggested that EGF/NF-κB signal may represent a novel therapeutic target for the treatment of human HA.
authors.affiliation: Department of Emergency, Peolpe's Hospital of Ningxia Hui Autonomous Region, Yinchuan 750002, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The People's Hospital of Zhongwei City of Ningxia Hui Autonomous Region, Zhongwei 755000, China.
authors.forename: Jingming
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Emergency, Peolpe's Hospital of Ningxia Hui Autonomous Region, Yinchuan 750002, China.
authors.forename: Zhanlong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Vascular Surgery, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan 750002, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Vascular Surgery, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan 750002, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Vascular Surgery, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan 750002, China. Electronic address: ouminghuinx@163.com.
authors.forename: Minghui
authors.initials: M
authors.lastname: Ou
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006391:Hemangioma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016328:NF-kappa B; D004815:Epidermal Growth Factor; D000071679:Glycogen Synthase Kinase 3 beta
keywords: EGF; Hemangioma; Invasion; NF-κB; Proliferation