Blockade of her2/neu decreases VEGF expression but does not alter HIF-1 distribution in experimental Wilms tumor
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- Published online on: September 1, 2003 https://doi.org/10.3892/or.10.5.1271
- Pages: 1271-1274
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Abstract
Her2/neu regulates angiogenesis in human breast cancer, in part by stabilizing hypoxia-inducible factor 1α (HIF-1α), causing accumulation of the HIF-1 heterodimer and thus increasing expression of the proangiogenic cytokine VEGF. Her2/neu has recently been shown to be overexpressed in a subset of Wilms tumors. Using her2/neu (+) and her2/neu (−) Wilms tumor cell lines, we tested the effect of blocking anti-her2/neu antibody in vitro and in vivo. Blocking antibody did not alter VEGF expression in vitro, but decreased expression of VEGF in her2/neu (+) Wilms tumor xenografts. Tumor suppression was less marked than in parallel experiments using agents directly blocking VEGF. HIF-1α immunostaining was not altered in her2/neu (+) xenografts exposed to blocking antibody. These results suggest that her2/neu contributes to Wilms tumor angiogenesis in vivo by regulating VEGF, but other processes may act to rescue HIF-1α and thus to support tumor growth in this system.
