Please use this identifier to cite or link to this item: http://hdl.handle.net/10201/56244

Title: Aberrant expression and association of VEGF and Dll4/Notch pathway molecules under hypoxia in patients with lung cancer
Issue Date: 2013
Publisher: F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología
Citation: Histology and Histopathology, vol. 28, nº 2, (2013)
ISSN: 1699-5848
0213-3911
Related subjects: CDU::6 - Ciencias aplicadas::61 - Medicina
Keywords: VEGF
Dll4
Notch
Abstract: Tumor angiogenesis plays important roles in the pathogenesis and prognosis of lung cancer. Both vascular endothelial growth factor (VEGF) and Dll4/Notch pathways are critical for angiogenesis, whereas their relationship under hypoxia in lung cancer remains unknown. Thus, in the present study, we evaluated the expression of VEGF and Dll4/Notch signaling molecules, and assessed their association with the microvessel density (CD31) and hypoxia (HIF1a) in lung cancer and normal lung tissues using immunohistochemical and Real-time RT-PCR techniques. Then, we investigated the biological function of Dll4 by transfecting Dll4 into HUVECs. In lung cancer tissues, Notch pathway molecules (HES1) and VEGF pathway molecules (VEGFR1 and VEGFR2) were significantly up-regulated, while the ratio of VEGFR1/VEGFR2 was decreased. CD31 and HIF1a were also found to be elevated in lung cancer. VEGFR1 was negatively correlated with Notch1 while positively correlated with Dll4. CD31 was positively correlated with HIF1a but negatively correlated with VEGFR1. Moreover, HIF1a was nearly positively correlated with HES1 in lung cancer tissues. After transfection, Dll4, Notch1 and VEGFR1 were up-regulated while VEGF and VEGFR2 were down-regulated in Dll4-transfected HUVECs compared with controls. Also, our findings suggest that the expression of VEGF and VEGFR2 increased gradually with the disease progression of lung cancer. In summary, VEGF and Notch signaling pathway molecules were overexpressed in lung cancer, which positively correlates with hypoxia (HIF1a) and angiogenesis (CD31). There might be a negative feedback loop between VEGF and Dll4/Notch signaling pathway in lung tumor angiogenesis.
Primary author: Yu, Shuang
Sun, Jianhua Sun
Zhang, Jingru
Xu, Xingfang
Li, Hong
Shan, Baozhong
Tian, Tian
Wang, Hongchun
Ma, Daoxin
Ji, Chunyan
URI: http://hdl.handle.net/10201/56244
Document type: info:eu-repo/semantics/article
Number of pages / Extensions: 8
Rights: info:eu-repo/semantics/openAccess
Appears in Collections:Vol.28, nº 2 (2013)

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