A role for Hox A5 in regulating angiogenesis and vascular patterning.
BACKGROUND
Homeobox (Hox) genes are transcriptional regulators which modulate embryonic morphogenesis and pathological tissue remodeling in adults via regulation of genes associated with cell-cell or cell extracellular matrix (ECM) interactions. We previously showed that while Hox 3 genes promote angiogenesis, Hox D10 inhibits this process.


RESULTS
Here we show that another Hox family gene, Hox A5, also blocks angiogenesis but accomplishes this by targeting different downstream genes than Hox D10. Sustained expression of Hox A5 leads to down regulation of many pro-angiogenic genes including VEGFR2, ephrin A1, Hif1alpha and COX-2. In addition, Hox A5 also upregulates expression of anti-angiogenic genes including Thrombospondin-2. Furthermore, we show that while Hox A5 mRNA is expressed in quiescent endothelial cells (EC), its expression is diminished or absent in active angiogenic EC found in association with breast tumors or in proliferating infantile hemangiomas.


CONCLUSIONS
Together our results suggest that restoring Hox A5 expression may provide a novel means to limit breast tumor growth or expansion of hemangiomas.
Rhoads
Kim
K
Surgical Research Laboratory, Dept of Surgery, University of California-San Francisco, San Francisco, CA 94143, USA.
Arderiu
Gemma
G
Charboneau
Aubri
A
Hansen
Scott L
SL
Hoffman
William
W
Boudreau
Nancy
N
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology; D006391:Hemangioma / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
C489213:HOXA5 protein, human; D018398:Homeodomain Proteins; D010750:Phosphoproteins; D016159:Tumor Suppressor Protein p53