Epidermal growth factor modulates the expression of vascular endothelial growth factor in the human prostate

The growth and dissemination of tumors in the body has been associated with angiogenesis. Vascular endothelial growth factor (VEGF) is an angiogenic f actor that stimulates endothelial cell growth and enhances vascular permeab ility. VEGF exerts its action by binding to specific cell surface receptors . Three receptors, VEGFR-1 (flt-1), VEGFR-2 (flk-1), and VEGFR-3 (flt-4) ha ve been identified. Very little information on the coordinated expression o f VEGF and its receptors in normal prostate, benign prostatic hyperplasia ( BPH), and prostate carcinoma is available. Therefore, we examined the immun ohistochemical localization of VEGF and its receptors in tissues derived fr om normal human prostate, BPH, and prostatic carcinoma. Immunostaining for VEGF was absent in the normal prostate. Epithelium lining the glands of pro state derived from patients with BPH exhibited strong immunostaining, The i ntensity of staining was relatively less in prostate carcinoma. It is inter esting that VEGFR-1 and VEGFR-3 were strongly expressed in both stromal and epithelial tissues in normal prostate, BPH, and carcinoma. In comparison, VEGFR-2 was not localized to normal prostate and its expression in the stro ma of BPH and epithelium of carcinoma was very weak. Because progression of prostate cancer is accompanied by altered expression of epidermal growth f actor (EGF) and its receptor (EGFR) in malignant cells, we investigated the effect of EGF on VEGF gene expression by Northern blot analysis in 2 human prostate cancer cell lines that express EGFR. EGF greatly enhanced the exp ression of VEGF messenger RNA in DU145 and PC3 cell lines in a dose-depende nt manner. The EGF induction of VEGF gene expression suggests a mechanism b y which angiogenesis could be accelerated in BPH and prostate carcinoma.