Characterization of the Role of Heyl in Angiogenesis and Breast Cancer Development

摘要

Neoangiogenesis process involves complex genetic expression alterations in endothelial cells. We performed SAGE analysis on purified endothelial cells from two freshly resected breast carcinoma and one normal breast tissue, finding that the expression of HEYL, a basic helix-loophelix (bHLH) transcription repressor, is consistently higher in the breast cancer libraries compared to normal breast tissue. Our in situ hybridization analysis using single sections and multi-tissue arrays validated the SAGE results. To investigate the effect of HEYL on endothelial cells, we infected human umbilical vein endothelial cell (HUVEC) using adenovirus expressing HEYL. We found that the expression of HEYL can increase HUVEC proliferation. Under serum starvation, the cells expressing HEYL showed strong anti-apoptosis ability compared to control cells. In addition, the HEYL expressing cells elongated 3 days after infection and showed actin rearrangement. These elongated cells have increased invasion ability in Boyden chamber assay. We found that PI-3 kinase signal transduction pathway involved in the cell invasion, since PI-3 kinase inhibitor can effectively block the invasion.