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Sustained expression of homeobox D10 inhibits angiogenesis.

ABSTRACT: Homeobox (Hox) genes are master regulatory genes that direct organogenesis and maintain differentiated tissue function. As HoxD3 and HoxB3 promote angiogenesis, we investigated whether endothelial cells use other Hox genes to maintain a mature quiescent phenotype. HoxD10 expression was higher in quiescent as compared to tumor-associated angiogenic endothelium. Microarray analysis of HoxD10-overexpressing endothelial cells revealed a pattern of gene expression consistent with a nonangiogenic phenotype. Moreover, sustained expression of HoxD10 impaired endothelial cell migration and blocked angiogenesis induced by basic fibroblast growth factor and vascular endothelial growth factor in the chick chorioallantoic membrane in vivo. HoxD10-overexpressing human endothelial cells also failed to form new vessels when implanted into immunocompromised mice. These results indicate a role for HoxD10 in maintaining a nonangiogenic state in the endothelium.

SUBMITTER: Myers C

PROVIDER: S-EPMC1850921 | biostudies-literature | 2002 Dec

REPOSITORIES: biostudies-literature

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Sustained expression of homeobox D10 inhibits angiogenesis.

Myers Connie C Charboneau Aubri A Cheung Irene I Hanks Douglas D Boudreau Nancy N

The American journal of pathology 20021201 6

Homeobox (Hox) genes are master regulatory genes that direct organogenesis and maintain differentiated tissue function. As HoxD3 and HoxB3 promote angiogenesis, we investigated whether endothelial cells use other Hox genes to maintain a mature quiescent phenotype. HoxD10 expression was higher in quiescent as compared to tumor-associated angiogenic endothelium. Microarray analysis of HoxD10-overexpressing endothelial cells revealed a pattern of gene expression consistent with a nonangiogenic phen ...[more]

PMID: 12466126

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Project description:Outer-shell s0/p0 orbital mixing with d10 orbitals and symmetry reduction upon cupriphication of cyclic trinuclear trigonal-planar gold(I) complexes are found to sensitize ground-state Cu(I)-Au(I) covalent bonds and near-unity phosphorescence quantum yields. Heterobimetallic Au4Cu2 {[Au4(?-C2,N3-EtIm)4Cu2(µ-3,5-(CF3)2Pz)2], (4a)}, Au2Cu {[Au2(?-C2,N3-BzIm)2Cu(µ-3,5-(CF3)2Pz)], (1) and [Au2(?-C2,N3-MeIm)2Cu(µ-3,5-(CF3)2Pz)], (3a)}, AuCu2 {[Au(?-C2,N3-MeIm)Cu2(µ-3,5-(CF3)2Pz)2], (3b) and [Au(?-C2,N3-EtIm)Cu2(µ-3,5-(CF3)2Pz)2], (4b)} and stacked Au3/Cu3 {[Au(?-C2,N3-BzIm)]3[Cu(µ-3,5-(CF3)2Pz)]3, (2)} form upon reacting Au3 {[Au(?-C2,N3-(N-R)Im)]3 ((N-R)Im = imidazolate; R = benzyl/methyl/ethyl = BzIm/MeIm/EtIm)} with Cu3 {[Cu(?-3,5-(CF3)2Pz)]3 (3,5-(CF3)2Pz = 3,5-bis(trifluoromethyl)pyrazolate)}. The crystal structures of 1 and 3a reveal stair-step infinite chains whereby adjacent dimer-of-trimer units are noncovalently packed via two Au(I)?Cu(I) metallophilic interactions, whereas 4a exhibits a hexanuclear cluster structure wherein two monomer-of-trimer units are linked by a genuine d10-d10 polar-covalent bond with ligand-unassisted Cu(I)-Au(I) distances of 2.8750(8) Å each-the shortest such an intermolecular distance ever reported between any two d10 centers so as to deem it a "metal-metal bond" vis-à-vis "metallophilic interaction." Density-functional calculations estimate 35-43 kcal/mol binding energy, akin to typical M-M single-bond energies. Congruently, FTIR spectra of 4a show multiple far-IR bands within 65-200 cm-1, assignable to vCu-Au as validated by both the Harvey-Gray method of crystallographic-distance-to-force-constant correlation and dispersive density functional theory computations. Notably, the heterobimetallic complexes herein exhibit photophysical properties that are favorable to those for their homometallic congeners, due to threefold-to-twofold symmetry reduction, resulting in cuprophilic sensitization in extinction coefficient and solid-state photoluminescence quantum yields approaching unity (?PL = 0.90-0.97 vs. 0-0.83 for Au3 and Cu3 precursors), which bodes well for potential future utilization in inorganic and/or organic LED applications.

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Sustained expression of homeobox D10 inhibits angiogenesis.

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Sustained expression of homeobox D10 inhibits angiogenesis.

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