XIAP-associated factor 1 (XAF1) suppresses angiogenesis in mouse endothelial cells.
OBJECTIVE
XIAP-associated factor 1 (XAF1) is a tumor suppressor gene, but its role in angiogenesis is unknown. We investigated whether XAF1 has any antiangiogenesis effect.


METHODS
MS1 (a mouse endothelial cell line) was infected with an adenoviral vector ZD55-XAF1. Controls were uninfected or infected with ZD55-EGFP. Wound healing assay and tube formation assay were used to assess angiogenesis. Cell proliferation was detected by WST-1 assay, and apoptosis was detected by TUNEL and APOPercentagetrade mark assays.


RESULTS
ZD55-XAF1 significantly upregulated XAF1, which was associated with decreased cell proliferation, migration and tube formation of MS1 cells. Ectopic overexpression of XAF1 induced apoptosis in MS1 and also sensitized cells to 5-fluorouracil-induced apoptosis. A significant decrease in the expression of Tie-1, Ang-1, Ang-2 and c-Myc was observed.


CONCLUSIONS
Our data suggest that XAF1 possesses a potential antiangiogenesis effect. Suppressed expression of Tie-1, Ang-1, Ang-2 and c-Myc may be mechanistically responsible for the observed antiangiogenesis effect.
Qiao
Liang
L
Department of Medicine, University of Hong Kong, Hong Kong, China.
Gu
Qing
Q
Dai
Yun
Y
Shen
Zan
Z
Liu
Xinyuan
X
Qi
Rong
R
Ma
Juan
J
Zou
Bing
B
Li
Zesong
Z
Lan
Hui Y
HY
Wong
Benjamin C Y
BC
D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae / Q000235:genetics; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D042810:Receptor, TIE-1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D044783:F-Box Proteins; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; C528956:XAF1 protein, mouse; D000804:Angiotensin II; D000803:Angiotensin I; D042810:Receptor, TIE-1