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.
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.
Pasquali
Daniela
D
Department of Clinical and Experimental Medicine and Surgery, Endocrine Unit, Second University of Napoli, Via Pansini 5, 80131 Napoli, Italy.
Rossi
Valentina
V
Staibano
Stefania
S
De Rosa
Gaetano
G
Chieffi
Paolo
P
Prezioso
Domenico
D
Mirone
Vincenzo
V
Mascolo
Massimo
M
Tramontano
Donatella
D
Bellastella
Antonio
A
Sinisi
Antonio Agostino
AA
D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000737:chemistry; D005768:Gastrointestinal Hormones / Q000032:analysis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009479:Neuropeptides / Q000032:analysis / Q000235:genetics*; D011467:Prostate / Q000737:chemistry; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D018000:Receptors, Peptide / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000032:analysis / Q000235:genetics*
D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C467610:PROK1 protein, human; C423608:PROK2 protein, human; C470837:PROKR1 protein, human; C470838:PROKR2 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived