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rdf:type |
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lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0017337,
umls-concept:C0018270,
umls-concept:C0026764,
umls-concept:C0033268,
umls-concept:C0086282,
umls-concept:C0215848,
umls-concept:C0302600,
umls-concept:C0441655,
umls-concept:C0567416,
umls-concept:C0851285,
umls-concept:C0965644,
umls-concept:C1314939,
umls-concept:C1333897,
umls-concept:C1426234,
umls-concept:C1704838,
umls-concept:C1999216,
umls-concept:C2003941
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pubmed:issue |
13
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pubmed:dateCreated |
2007-12-6
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pubmed:abstractText |
Angiogenesis has a critical role in the pathophysiology of multiple myeloma (MM); however, the molecular mechanisms underlying this process are not completely elucidated. The new tumor-suppressor gene inhibitor of growth family member 4 (ING4) has been recently implicated in solid tumors as a repressor of angiogenesis. In this study, we found that ING4 expression in MM cells was correlated with the expression of the proangiogenic molecules interleukin-8 (IL-8) and osteopontin (OPN). Moreover, we demonstrate that ING4 suppression in MM cells up-regulated IL-8 and OPN, increasing the hypoxia inducible factor-1alpha (HIF-1alpha) activity and its target gene NIP-3 expression in hypoxic condition. In turn, we show that the inhibition of HIF-1alpha by siRNA suppressed IL-8 and OPN production by MM cells under hypoxia. A direct interaction between ING4 and the HIF prolyl hydroxylase 2 (HPH-2) was also demonstrated. Finally, we show that ING4 suppression in MM cells significantly increased vessel formation in vitro, blunted by blocking IL-8 or OPN. These in vitro observations were confirmed in vivo by finding that MM patients with high IL-8 production and microvascular density (MVD) have significantly lower ING4 levels compared with those with low IL-8 and MVD. Our data indicate that ING4 exerts an inhibitory effect on the production of proangiogenic molecules and consequently on MM-induced angiogenesis.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0006-4971
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pubmed:author |
pubmed-author:BonatiAntonioA,
pubmed-author:BonominiSabrinaS,
pubmed-author:CollaSimonaS,
pubmed-author:DonofrioGaetanoG,
pubmed-author:FerrariLucaL,
pubmed-author:GiulianiNicolaN,
pubmed-author:GrecoAngelaA,
pubmed-author:LadettoMarcoM,
pubmed-author:LazzarettiMircaM,
pubmed-author:LunghiPaoloP,
pubmed-author:ManciniCristinaC,
pubmed-author:MangoniMarcellinaM,
pubmed-author:MartoranaDavideD,
pubmed-author:MazzeraLauraL,
pubmed-author:MirandaClaudiaC,
pubmed-author:MorandiFrancescaF,
pubmed-author:NeriAntoninoA,
pubmed-author:NeriTauro MariaTM,
pubmed-author:RavanettiLaraL,
pubmed-author:RizzoliVittorioV,
pubmed-author:TagliaferriSaraS
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
110
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4464-75
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pubmed:dateRevised |
2008-9-30
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pubmed:meshHeading |
pubmed-meshheading:17848618-Aged,
pubmed-meshheading:17848618-Angiogenic Proteins,
pubmed-meshheading:17848618-Bone Marrow Examination,
pubmed-meshheading:17848618-Cell Cycle Proteins,
pubmed-meshheading:17848618-Cell Line, Tumor,
pubmed-meshheading:17848618-Homeodomain Proteins,
pubmed-meshheading:17848618-Humans,
pubmed-meshheading:17848618-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:17848618-Interleukin-8,
pubmed-meshheading:17848618-Middle Aged,
pubmed-meshheading:17848618-Multiple Myeloma,
pubmed-meshheading:17848618-Neovascularization, Pathologic,
pubmed-meshheading:17848618-Osteopontin,
pubmed-meshheading:17848618-Tumor Suppressor Proteins
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pubmed:year |
2007
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pubmed:articleTitle |
The new tumor-suppressor gene inhibitor of growth family member 4 (ING4) regulates the production of proangiogenic molecules by myeloma cells and suppresses hypoxia-inducible factor-1 alpha (HIF-1alpha) activity: involvement in myeloma-induced angiogenesis.
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pubmed:affiliation |
Hematology and Bone Marrow Transplantation Center, University of Parma, Parma, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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