Abstract 30: Modulating the angiogenic potential of human microvascular endothelial cells by an endogenous zinc finger transcription factor, ZNF24

Angiogenesis, the formation of new blood vessels from preexisting ones, is an indispensible process under normal physiological conditions such as embryonic development, certain stages of the female reproductive cycle and placenta formation during pregnancy as well as under pathological conditions such as wound healing, diabetic retinopathy, and cancer initiation, progression and metastasis. We have previously identified the molecular mechanism by which a zinc finger transcription factor, ZNF24, functions as a new inhibitor of tumor angiogenesis. ZNF24 represses the transcription of vascular endothelial growth factor (VEGF) in breast cancer cells via direct binding to an 11-bp fragment within the VEGF proximal promoter. In the current study, we have focused on the role of ZNF24 in modulating the angiogenic potential of the endothelial compartment of the tumor microenvironment. Utilizing primary human microvascular endothelial cells, we have found that silencing ZNF24 in these cells leads to significantly decreased endothelial cell proliferation. Quantitative real-time PCR array analyses have identified multiple cell cycle regulators as potential downstream targets of ZNF24, which may be responsible for the decreased proliferation in these cells. Moreover, knockdown of ZNF24 in microvascular endothelial cells leads to significantly decreased cell migration and invasion. Consistently, we found that VEGFR2 signaling and the proteolytic activity of matrix metalloproteinase-2 (MMP2...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor Biology Source Type: research