title: Inhibition of endothelial cell proliferation and tumor angiogenesis by up-regulating NDRG2 expression in breast cancer cells.
abstract: The N-myc downstream-regulated gene 2 (NDRG2) is involved in tumor cell differentiation and apoptosis, but its function in tumor angiogenesis remains to be established. Here, we employed adenovirus overexpressing NDRG2 (Ad-NDRG2) to efficiently up-regulate target gene expression in the NDRG2-low-expressing, breast cancer cell line MCF-7. Moreover, VEGF secretion was decreased in MCF-7 cells infected by Ad-NDRG2, and medium conditioned by these infected cells could significantly inhibit the proliferation, tube formation and invasion of human umbilical vein endothelial cells (HUVECs). Further study indicated that the angiogenesis promoting factors VEGF and HIF-1α were down-regulated, whereas the angiogenesis suppressing factors p53 and VHL were up-regulated in MCF-7 cells infected by Ad-NDRG2. Finally, in a nude mouse model, intratumoral injections of Ad-NDRG2 every 3 days for 20 days significantly inhibited the growth and angiogenesis of xenografted MCF-7 tumors. In summary, these data indicate that NDRG2 may be involved in angiogenesis by impacting the expression of angiogenesis related factors. Thus, specific overexpression of NDRG2 by adenovirus represents a promising approach for the treatment of tumor angiogenesis.
authors.affiliation: Department of Oncology, Xijing Hospital, The State Key Discipline of Cell Biology, The Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.forename: Wenchao
authors.initials: W
authors.lastname: Liu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yan
authors.forename: Qianrong
authors.initials: Q
authors.lastname: Wang
authors.forename: Qingli
authors.initials: Q
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Xue
authors.forename: Hui
authors.initials: H
authors.lastname: Ren
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.forename: Yuanxiong
authors.initials: Y
authors.lastname: Cheng
authors.forename: Sen
authors.initials: S
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Miao
authors.forename: Libo
authors.initials: L
authors.lastname: Yao
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology*; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D015854:Up-Regulation