Pasquali Daniela, Rossi Valentina, Staibano Stefania, De Rosa Gaetano, Chieffi Paolo, Prezioso Domenico, Mirone Vincenzo, Mascolo Massimo, Tramontano Donatella, Bellastella Antonio, Sinisi Antonio Agostino
Department of Clinical and Experimental Medicine and Surgery, Endocrine Unit, Second University of Napoli, Via Pansini 5, 80131 Napoli, Italy.
Endocrinology. 2006 Sep;147(9):4245-51. doi: 10.1210/en.2006-0614. Epub 2006 Jun 8.
A new family of angiogenic factors named endocrine-gland-derived vascular endothelial growth factors (EG-VEGF)/prokineticins (PK) have been recently described as predominantly expressed in steroidogenic tissues. Whether the normal and malignant epithelial prostate cells and tissues express EG-VEGF/PK1 and PK2 and their receptors is still unknown. We studied the expression of EG-VEGF/PK1 and PK2 and their receptors (PK-R1 and PK-R2) in human prostate and their involvement in cancer. Using immunohistochemistry, Western blot, and RT-PCR, we determined the expression of EG-VEGF/PK1 in normal prostate (NP) and malignant prostate tissues (PCa), in epithelial cell primary cultures from normal prostate (NPEC) and malignant prostate (CPEC) and in a panel of prostate cell lines. In NPEC, CPEC, and in EPN, a nontransformed human prostate epithelial cell line, EG-VEGF/PK1, PK2, PK-R1, and PK-R2 mRNA levels were evaluated by quantitative RT-PCR. EG-VEGF/PK1 transcript was found in PCa, in CPEC, in EPN, and in LNCaP, whereas it was detected at low level in NP and in NPEC. EG-VEGF/PK1 was absent in androgen-independent PC3 and DU-145 cell lines. Immunochemistry confirmed that EG-VEGF/PK1 protein expression was restricted to hyperplastic and malignant prostate tissues, localized in the glandular epithelial cells, and progressively increased with the prostate cancer Gleason score advancement. EG-VEGF/PK1 and PK2 were weakly expressed in NPEC and EPN. On the other hand, their transcripts were highly detected in CPEC. PK-R1 and PK-R2 were found in NPEC, EPN, and CPEC. Interestingly, CPEC showed a significantly (P < 0.05) higher expression of EG-VEGF/PK1, PK2, PK-R1, and PK-R2 compared with NPEC and EPN. We demonstrated that PKs and their receptors are expressed in human prostate and that their levels increased with prostate malignancy. It may imply that EG-VEGF/PK1 could be involved in prostate carcinogenesis, probably regulating angiogenesis. Thus, the level of EG-VEGF/PK1 could be useful for prostate cancer outcome evaluation and as a target for prostate cancer treatment in the future.
最近发现了一个新的血管生成因子家族，即内分泌腺源性血管内皮生长因子（EG-VEGF）/促动力蛋白（PK），主要在类固醇生成组织中表达。正常和恶性前列腺上皮细胞及组织是否表达EG-VEGF/PK1和PK2及其受体仍不清楚。我们研究了EG-VEGF/PK1和PK2及其受体（PK-R1和PK-R2）在人前列腺中的表达及其与癌症的关系。我们使用免疫组织化学、蛋白质印迹和逆转录-聚合酶链反应（RT-PCR），测定了EG-VEGF/PK1在正常前列腺（NP）和恶性前列腺组织（PCa）、来自正常前列腺（NPEC）和恶性前列腺（CPEC）的上皮细胞原代培养物以及一组前列腺细胞系中的表达。在NPEC、CPEC以及非转化的人前列腺上皮细胞系EPN中，通过定量RT-PCR评估了EG-VEGF/PK1、PK2、PK-R1和PK-R2的mRNA水平。在PCa、CPEC、EPN和LNCaP中发现了EG-VEGF/PK1转录本，而在NP和NPEC中检测到的水平较低。在雄激素非依赖性PC3和DU-145细胞系中未检测到EG-VEGF/PK1。免疫组织化学证实，EG-VEGF/PK1蛋白表达仅限于增生性和恶性前列腺组织，定位于腺上皮细胞中，并随着前列腺癌Gleason评分的升高而逐渐增加。EG-VEGF/PK1和PK2在NPEC和EPN中表达较弱。另一方面，在CPEC中高度检测到它们（EG-VEGF/PK1和PK2）的转录本。在NPEC、EPN和CPEC中发现了PK-RI和PK-R2。有趣的是，与NPEC和EPN相比，CPEC中EG-VEGF/PK1、PK2、PK-R1和PK-R2的表达显著更高（P<0.05）。我们证明了PK及其受体在人前列腺中表达，且其水平随着前列腺恶性程度的增加而升高。这可能意味着EG-VEGF/PK1可能参与前列腺癌的发生，可能调节血管生成。因此，EG-VEGF/PK1的水平可能有助于前列腺癌预后评估，并在未来作为前列腺癌治疗的靶点。
