Epidermal growth factor modulates the expression of vascular endothelial growth factor in the human prostate.
Epidermal growth factor modulates the expression of vascular endothelial growth factor in the human prostate.
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DOI：
10.1002/j.1939-4640.2001.tb02199.x
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发表时间：
2001-05
影响因子：
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通讯作者：
N. Ravindranath;D. Wion;P. Brachet;D. Djakiew
中科院分区：
文献类型：
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作者：
N. Ravindranath;D. Wion;P. Brachet;D. Djakiew
肿瘤在体内的生长和扩散与血管生成有关。血管内皮生长因子（VEGF）是一种血管生成因子，可刺激内皮细胞生长并增强血管通透性。VEGF通过与特定细胞表面受体结合来发挥其作用。已经鉴定了三种受体，VEGFR-1（flt-1）、VEGFR-2（flk-1）和VEGFR-3（flt-4）。关于VEGF及其受体在正常前列腺、良性前列腺增生（BPH）和前列腺癌中的协调表达的信息非常少。因此，我们研究了VEGF及其受体在正常人前列腺、BPH和前列腺癌组织中的免疫组织化学定位。VEGF的免疫染色在正常前列腺中不存在。前列腺增生患者前列腺上皮细胞呈强阳性染色。前列腺癌的染色强度相对较低。有趣的是，VEGFR-1和VEGFR-3在正常前列腺、BPH和癌的间质和上皮组织中均强烈表达。VEGFR-2在正常前列腺组织中不表达，在BPH间质和癌组织上皮中表达较弱。由于前列腺癌的进展伴随着表皮生长因子（EGF）及其受体（EGFR）在恶性细胞中表达的改变，我们通过北方印迹分析在表达EGFR的2个人前列腺癌细胞系中研究EGF对VEGF基因表达的影响。EGF可显著增强DU 145和PC 3细胞VEGF mRNA的表达，且呈剂量依赖性。EGF对VEGF基因表达的诱导提示了BPH和前列腺癌中血管生成的加速机制。
The growth and dissemination of tumors in the body has been associated with angiogenesis. Vascular endothelial growth factor (VEGF) is an angiogenic factor that stimulates endothelial cell growth and enhances vascular permeability. 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) have been identified. Very little information on the coordinated expression of VEGF and its receptors in normal prostate, benign prostatic hyperplasia (BPH), and prostate carcinoma is available. Therefore, we examined the immunohistochemical localization of VEGF and its receptors in tissues derived from normal human prostate, BPH, and prostatic carcinoma. Immunostaining for VEGF was absent in the normal prostate. Epithelium lining the glands of prostate derived from patients with BPH exhibited strong immunostaining. The intensity of staining was relatively less in prostate carcinoma. It is interesting 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 stroma of BPH and epithelium of carcinoma was very weak. Because progression of prostate cancer is accompanied by altered expression of epidermal growth factor (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 expression of VEGF messenger RNA in DU145 and PC3 cell lines in a dose-dependent manner. The EGF induction of VEGF gene expression suggests a mechanism by which angiogenesis could be accelerated in BPH and prostate carcinoma.