title: Up-regulation of pVHL along with down-regulation of HIF-1α by NDRG2 expression attenuates proliferation and invasion in renal cancer cells.
abstract: The majority of renal cell carcinomas (RCCs) are characterized by loss of function of the tumor suppressor gene von Hippel Lindau (VHL), which acts as ubiquitin ligase for hypoxia-inducible factor-1α (HIF-1α). In the absence of VHL, HIF-1α protein becomes stabilized and contributes to tumorigenesis. Recent data demonstrate the antitumor efficacy of VHL promoter in RCC cells. This study demonstrates that N-Myc downstream-regulated gene 2 (NDRG2) is a potential regulator of VHL. NDRG2 is involved in proliferation and invasion of cancer cell, furthermore it is frequently down-regulated in renal cell carcinoma. Herein we evaluated the effect of NDRG2 overexpression on proliferation and invasion in human renal cancer cells. The human renal cancer cell line 786-O and A498 were infected with Ad-NDRG2 or Ad-LacZ. Overexpression of NDRG2 not only inhibited the growth of the cells, but also suppressed the invasion. Further study showed that the tumor suppressor gene VHL were up-regulated, whereas transcription factor HIF-1a and vascular endothelial growth factor (VEGF) were down-regulated in 786-O cells infected by Ad-NDRG2. Finally, in a nude mouse model, intratumoral injections of Ad-NDRG2 every 3 days for a total of seven times significantly inhibited the growth and angiogenesis of xenografted 786-O tumors. In conclusion, these data indicate that NDRG2 may be involved in proliferation and invasion by impacting the expression of VHL and HIF-1α. NDRG2 may be an attractive therapeutic target for renal cell carcinoma.
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, the Fourth Military Medical University, Xi'an, China ; Department of Urology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China ; Department of Urology, Wuhan General Hospital, Guangzhou Command PLA, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Urology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Guo-jun
authors.initials: GJ
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Hainan Branch of PLA General Hospital, Sanya, China.
authors.forename: Ming-zhi
authors.initials: MZ
authors.lastname: Shen
authors.affiliation: Department of Urology, Wuhan General Hospital, Guangzhou Command PLA, Wuhan, China.
authors.forename: Tie-jun
authors.initials: TJ
authors.lastname: Pan
authors.affiliation: Department of Urology, Armed Police General Hospital, Beijing, China.
authors.forename: Chui-gong
authors.initials: CG
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, the Fourth Military Medical University, Xi'an, China.
authors.forename: Qin-hao
authors.initials: QH
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, the Fourth Military Medical University, Xi'an, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ru
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, the Fourth Military Medical University, Xi'an, China.
authors.forename: Xi-ping
authors.initials: XP
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, the Fourth Military Medical University, Xi'an, China.
authors.forename: Tian-shui
authors.initials: TS
authors.lastname: Niu
authors.affiliation: Department of Urology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Guo-dong
authors.initials: GD
authors.lastname: Wang
authors.affiliation: Department of Urology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wei
authors.affiliation: Department of Urology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Rui-xiao
authors.initials: RX
authors.lastname: Li
authors.affiliation: Department of Urology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Urology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, the Fourth Military Medical University, Xi'an, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li