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.
Methods and 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, Hif1α 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
