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EAF2 loss enhances angiogenic effects of Von Hippel-Lindau heterozygosity on the murine liver and prostate
Pascal, Laura E.; Ai, Junkui; Rigatti, Lora H.; Lipton, Anne K.; Xiao, Wuhan; Gnarra, James R.; Wang, Zhou; Wang, Z (reprint author), Univ Pittsburgh, Sch Med, Dept Urol, Suite G40,5200 Ctr Ave, Pittsburgh, PA 15232 USA; pascalle@upmc.edu; aij@upmc.edu; rigattil@pitt.edu; liptonak@upmc.edu; w-xiao@ihb.ac.cn; gnarrajr@upmc.edu; wangz2@upmc.edu
2011
Source PublicationANGIOGENESIS
ISSN0969-6970
Volume14Issue:3Pages:331-343
AbstractVon Hippel-Lindau (VHL) disease results from the inactivation of the VHL gene and is characterized by highly vascular tumors. A consequence of VHL loss is the stabilization of hypoxia-inducible factor (HIF) alpha subunits and increased expression of HIF target genes, which include pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF). In mice, homozygous deletion of VHL is embryonic lethal due to vascular abnormalities in the placenta; and, VHL(+/-) mice develop proliferative vascular lesions in several major organs, most prominently the liver. Loss of ELL-associated factor (EAF2) in murine models has also been shown to induce increased vascular density in the liver as well as the prostate. Previously, EAF2 was determined to be a binding partner of VHL and loss of EAF2 induced a reduction in pVHL levels and an increase in hypoxia induced factor 1 alpha (HIF1 alpha) levels in vitro. Here we characterized the cooperative effects of VHL- and EAF2-deficiency on angiogenesis in the liver and prostate of male mice. VHL deficiency consistently increased the incidence of hepatic vascular lesions across three mouse strains. These vascular lesions where characterized by an increase in microvessel density, and staining intensity of VHL target proteins HIF1 alpha and VEGF. EAF2(-/-)VHL(+/-) mice had increased incidence of proliferative hepatic vascular lesions (4/4) compared to VHL(+/-) (10/18) and EAF2(-/-) (0/5) mice. Prostates of EAF2(-/-)VHL(+/-) mice also displayed an increase in microvessel density, as well as stromal inflammation and prostatic intraepithelial neoplasia. These results suggest that cooperation of VHL and EAF2 may be critical for angiogenic regulation of the liver and prostate, and concurrent loss of these two tumor suppressors may result in a pro-angiogenic phenotype.
KeywordVon Hippel-lindau (Vhl) Ell-associated Factor 2 (Eaf2) Hepatic Vascular Lesion Prostatic Intraepithelial Neoplasia (Pin)
Department[Pascal, LE; Ai, JK; Lipton, AK; Xiao, WH; Gnarra, JR; Wang, Z] Univ Pittsburgh, Sch Med, Dept Urol, Pittsburgh, PA 15232 USA; [Rigatti, LH] Univ Pittsburgh, Div Lab Anim Resources, Univ Pittsburgh Canc Inst, Pittsburgh, PA 15261 USA; [Xiao, WH] Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China; [Lipton, AK; Wang, Z] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15232 USA
Subject AreaCardiovascular System & Cardiology
Funding Organization[T32 DK007774]; [R37 DK51193]; [R01CA120386]; [CA78335]; [CA125930] ; [T32 DK007774]; [R37 DK51193]; [R01CA120386]; [CA78335]; [CA125930] ; [T32 DK007774]; [R37 DK51193]; [R01CA120386]; [CA78335]; [CA125930] ; [T32 DK007774]; [R37 DK51193]; [R01CA120386]; [CA78335]; [CA125930]
Indexed BySCI
Language英语
WOS IDWOS:000293922300010
Funding Organization[T32 DK007774]; [R37 DK51193]; [R01CA120386]; [CA78335]; [CA125930] ; [T32 DK007774]; [R37 DK51193]; [R01CA120386]; [CA78335]; [CA125930] ; [T32 DK007774]; [R37 DK51193]; [R01CA120386]; [CA78335]; [CA125930] ; [T32 DK007774]; [R37 DK51193]; [R01CA120386]; [CA78335]; [CA125930]
Citation statistics
Cited Times:13[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/16353
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorWang, Z (reprint author), Univ Pittsburgh, Sch Med, Dept Urol, Suite G40,5200 Ctr Ave, Pittsburgh, PA 15232 USA; pascalle@upmc.edu; aij@upmc.edu; rigattil@pitt.edu; liptonak@upmc.edu; w-xiao@ihb.ac.cn; gnarrajr@upmc.edu; wangz2@upmc.edu
Recommended Citation
GB/T 7714
Pascal, Laura E.,Ai, Junkui,Rigatti, Lora H.,et al. EAF2 loss enhances angiogenic effects of Von Hippel-Lindau heterozygosity on the murine liver and prostate[J]. ANGIOGENESIS,2011,14(3):331-343.
APA Pascal, Laura E..,Ai, Junkui.,Rigatti, Lora H..,Lipton, Anne K..,Xiao, Wuhan.,...&wangz2@upmc.edu.(2011).EAF2 loss enhances angiogenic effects of Von Hippel-Lindau heterozygosity on the murine liver and prostate.ANGIOGENESIS,14(3),331-343.
MLA Pascal, Laura E.,et al."EAF2 loss enhances angiogenic effects of Von Hippel-Lindau heterozygosity on the murine liver and prostate".ANGIOGENESIS 14.3(2011):331-343.
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