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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • Epithelial Cells / chemistry
  • Gastrointestinal Hormones / analysis
  • Gastrointestinal Hormones / genetics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Immunohistochemistry
  • Male
  • Neuropeptides / analysis
  • Neuropeptides / genetics*
  • Prostate / chemistry
  • Prostatic Hyperplasia / metabolism
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / metabolism*
  • RNA, Messenger / analysis
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, Peptide / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation
  • Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / analysis
  • Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / genetics*


  • Gastrointestinal Hormones
  • Neuropeptides
  • PROK1 protein, human
  • PROK2 protein, human
  • PROKR1 protein, human
  • PROKR2 protein, human
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide
  • Vascular Endothelial Growth Factor, Endocrine-Gland-Derived