EXPRESSION AND MODULATION OF HOMEOBOX GENES FROM CLUSTER-B IN ENDOTHELIAL-CELLS

Angiogenesis is a complex phenomenon likely to be under the strict con trol of a group of transcription factor(s). Homeobox (HOX)-containing proteins have been identified as regulators controlling the coordinate d expression of genes involved in organ development and tissue differe ntiation. In this study, we have demonstrated that human umbilical vei n endothelial cells (HUVEC) express 8 of the 10 HOX genes contained in cluster B. Treatment of HUVEC with tissue plasminogen activator (TPA) , an agent known to induce morphologic changes in endothelial cells, o r vascular endothelium growth factor (VEGF), a proliferative and angio genesis inducer, results in a specific time-dependent modulation of th e eight HOX genes identified. Interestingly, neither basic fibroblast growth factor, an endothelial proliferative agent, nor TNP-470, a fuma gillin derivative with potent antiendothelial cell proliferation prope rties, affected expression of these HOX genes. Specific modulation of HOX genes by differentiating agents but not by proliferative or antipr oliferative molecules suggests that they could be involved in the cont rol of the genetic program that coordinates the construction of new bl ood vessels.