Endothelial p21^WAF1/Cip1 Cell Cycle Inhibitor is Down-regulated in Breast Cancer

Abstract

Background: Tumor angiogenesis is considered a multi-pathway process, while p21^WAF1/Cip1 is a CDK inhibitor involved in cell division and survival. Herein the tumor environment effect on endothelial p21^WAF1/Cip1 expression is examined. Materials and Methods: The EA.hy 926 endothelial cell line and tumor-conditioned medium (TCM) from the MDA-MB-468 breast cancer cell line were used. Endothelial cells grown alone and in TCM were immunostained for p21^WAF1/Cip1 and analyzed by RT-PCR. Forty-four cases of breast cancer and forty-three cases of normal breast tissue were immunostained for p21^WAF1/Cip1. Results: Endothelial p21^WAF1/Cip1 is transcriptionally down-regulated under the influence of TCM. Moreover, it seems that breast cancer tumor endothelium does not express p21^WAF1/Cip1. Conclusion: P21^WAF1/Cip1 plays a major role in angiogenesis, since tumor cells seem to down-regulate endothelial p21^WAF1/Cip1, compared to endothelial cells grown in serum-free medium. The verification of the tissue culture experiment results by immunohistochemistry on tissue sections indicates p21^WAF1/Cip1 as a target of modern molecular therapy.