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This version published online on June 8, 2006
Endocrinology, doi:10.1210/en.2006-0614
A more recent version of this article appeared on September 1, 2006
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Submitted on May 8, 2006
Accepted on May 30, 2006

The Endocrine Gland Derived Vascular Endothelial Growth Factor (EG-VEGF) /Prokineticin 1 And 2 And Receptor Expression In Human Prostate: Up-Regulation Of EG-VEGF /Prokineticin 1 With Malignancy

Daniela Pasquali, Valentina Rossi, Stefania Staibano, Gaetano De Rosa, Paolo Chieffi, Domenico Prezioso, Vincenzo Mirone, Massimo Mascolo, Donatella Tramontano, Antonio Bellastella, and Antonio Agostino Sinisi*

Department of Clinical and Experimental Medicine and Surgery, Endocrine Unit, (Da.P., V.R., A. B., A.A.S); Second University of Naples; Department of Biomorphological and Functional Sciences, Pathology Section (S.S, G.DR, M.M.), Urologic Clinic (D.P., V.M.), Department of Biology and Molecular Pathology (D.T.), University of Naples Federico II, Department of Experimental Medicine (P.C.) Second University of Naples, Naples, Italy

* To whom correspondence should be addressed. E-mail: antonio.sinisi{at}unina2.it.

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 determine the expression of EG-VEGF/PK1 in normal (NP) and malignant prostate tissues (PCa), in epithelial cell primary cultures from normal (NPEC) and malignant prostates (CPEC), and in a panel of prostate cell lines. In NPEC, CPEC and in EPN, a non-transformed 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, while 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, PKR-1 and 2 compared with NPEC and EPN. We demonstrated that PKs and their receptors are expressed in human prostate and 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 target for prostate cancer treatment in the future.
Key words: EG-VEGF • PK-R1 • PK-R2 • prostate cancer • EPN




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