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Gene Review

PROK1  -  prokineticin 1

Homo sapiens

Synonyms: EG-VEGF, EGVEGF, Endocrine-gland-derived vascular endothelial growth factor, Mambakine, PK1, ...
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Disease relevance of PROK1


High impact information on PROK1


Chemical compound and disease context of PROK1

  • When the EG-VEGF gene-overexpressing colorectal cancer cell line that had been treated with phosphorothioate antisense EG-VEGF oligonucleotides was injected s.c. into mice, angiogenesis and tumor growth were inhibited [9].
  • Phase I/II clinical trials involving N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin (PK1; FCE28068) showed a four- to fivefold reduction in anthracycline-related toxicity, and, despite cumulative doses up to 1680 mg/m2 (doxorubicin equivalent), no cardiotoxicity was observed [10].
  • The aim of this study was to establish a subcellular fractionation method for B16F10 murine melanoma cells and subsequently to use it to define the intracellular trafficking of N-(2-hydroxyproplylmethacrylamide) (HPMA) copolymer-bound doxorubicin (PK1) [11].

Biological context of PROK1

  • Expression of PK1 was elevated in the secretory compared with the proliferative phase of the menstrual cycle (P < 0.05) [12].
  • EG-VEGF is mainly localized to the syncytiotrophoblast layer with the highest expression detected between the 8th and 10th wk of gestation [2].
  • These findings suggest that EG-VEGF has a direct effect on TCs via its receptor PKR1 and is likely to play an important role in human placentation [2].
  • Therefore, while the MIT-like ACTX family appears to adopt the ancestral disulfide-directed beta-hairpin protein fold of MIT1, a motif believed to be shared by other AVIT family peptides, variations in the amino acid sequence and surface charge result in a loss of activity on prokineticin receptors [13].
  • 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 [4].

Anatomical context of PROK1


Associations of PROK1 with chemical compounds

  • Treatment with 1 microM ( micromol/liter(-1)) progesterone resulted in 2.91 +/- 0.75-fold elevation in PK1 expression, compared with controls (P < 0.05) [12].
  • 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 [4].
  • In in vitro endometrial cell culture, EG-VEGF mRNA was detected in endometrial cells only in the presence of steroids, suggesting that EG-VEGF expression is highly dependent on the steroid hormones [3].
  • EG-VEGF/PK1 was absent in androgen-independent PC3 and DU-145 cell lines [4].
  • The t1/2 for oral calcitriol was 38 +/- 14 h for PK1 and 30 +/- 4 h for PK2 (not significant (NS)) [14].
  • COX-2 mRNA and protein expression, and prostaglandin synthesis, were elevated in response to treatment with PROK1 [15].

Physical interactions of PROK1

  • Consistent with such an expression pattern, the human EG-VEGF gene promoter has a potential binding site for steroidogenic factor (SF)-1, a pivotal element for steroidogenic-specific transcription [16].

Regulatory relationships of PROK1


Other interactions of PROK1


Analytical, diagnostic and therapeutic context of PROK1


  1. Presence and regulation of endocrine gland vascular endothelial growth factor/prokineticin-1 and its receptors in ovarian cells. Kisliouk, T., Levy, N., Hurwitz, A., Meidan, R. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  2. Expression and oxygen regulation of endocrine gland-derived vascular endothelial growth factor/prokineticin-1 and its receptors in human placenta during early pregnancy. Hoffmann, P., Feige, J.J., Alfaidy, N. Endocrinology (2006) [Pubmed]
  3. Endocrine gland-derived vascular endothelial growth factor is expressed in human peri-implantation endometrium, but not in endometrial carcinoma. Ngan, E.S., Lee, K.Y., Yeung, W.S., Ngan, H.Y., Ng, E.H., Ho, P.C. Endocrinology (2006) [Pubmed]
  4. 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. Pasquali, D., Rossi, V., Staibano, S., De Rosa, G., Chieffi, P., Prezioso, D., Mirone, V., Mascolo, M., Tramontano, D., Bellastella, A., Sinisi, A.A. Endocrinology (2006) [Pubmed]
  5. Expression of endocrine gland-derived vascular endothelial growth factor in ovarian carcinoma. Zhang, L., Yang, N., Conejo-Garcia, J.R., Katsaros, D., Mohamed-Hadley, A., Fracchioli, S., Schlienger, K., Toll, A., Levine, B., Rubin, S.C., Coukos, G. Clin. Cancer Res. (2003) [Pubmed]
  6. Implications of endocrine gland-derived vascular endothelial growth factor/prokineticin-1 signaling in human neuroblastoma progression. Ngan, E.S., Sit, F.Y., Lee, K., Miao, X., Yuan, Z., Wang, W., Nicholls, J.M., Wong, K.K., Garcia-Barcelo, M., Lui, V.C., Tam, P.K. Clin. Cancer Res. (2007) [Pubmed]
  7. Identification of an angiogenic mitogen selective for endocrine gland endothelium. LeCouter, J., Kowalski, J., Foster, J., Hass, P., Zhang, Z., Dillard-Telm, L., Frantz, G., Rangell, L., DeGuzman, L., Keller, G.A., Peale, F., Gurney, A., Hillan, K.J., Ferrara, N. Nature (2001) [Pubmed]
  8. Bv8 and endocrine gland-derived vascular endothelial growth factor stimulate hematopoiesis and hematopoietic cell mobilization. LeCouter, J., Zlot, C., Tejada, M., Peale, F., Ferrara, N. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  9. Angiogenesis and tumor proliferation/metastasis of human colorectal cancer cell line SW620 transfected with endocrine glands-derived-vascular endothelial growth factor, as a new angiogenic factor. Goi, T., Fujioka, M., Satoh, Y., Tabata, S., Koneri, K., Nagano, H., Hirono, Y., Katayama, K., Hirose, K., Yamaguchi, A. Cancer Res. (2004) [Pubmed]
  10. Polymer-drug conjugates: towards a novel approach for the treatment of endrocine-related cancer. Duncan, R., Vicent, M.J., Greco, F., Nicholson, R.I. Endocr. Relat. Cancer (2005) [Pubmed]
  11. Establishment of subcellular fractionation techniques to monitor the intracellular fate of polymer therapeutics I. Differential centrifugation fractionation B16F10 cells and use to study the intracellular fate of HPMA copolymer-doxorubicin. Philipp Seib, F., Jones, A.T., Duncan, R. Journal of drug targeting (2006) [Pubmed]
  12. Expression and regulation of the prokineticins (endocrine gland-derived vascular endothelial growth factor and Bv8) and their receptors in the human endometrium across the menstrual cycle. Battersby, S., Critchley, H.O., Morgan, K., Millar, R.P., Jabbour, H.N. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  13. Discovery of an MIT-like atracotoxin family: spider venom peptides that share sequence homology but not pharmacological properties with AVIT family proteins. Wen, S., Wilson, D.T., Kuruppu, S., Korsinczky, M.L., Hedrick, J., Pang, L., Szeto, T., Hodgson, W.C., Alewood, P.F., Nicholson, G.M. Peptides (2005) [Pubmed]
  14. Pharmacokinetics and efficacy of pulse oral versus intravenous calcitriol in hemodialysis patients. Levine, B.S., Song, M. J. Am. Soc. Nephrol. (1996) [Pubmed]
  15. Prokineticin 1 signaling and gene regulation in early human pregnancy. Evans, J., Catalano, R.D., Morgan, K., Critchley, H.O., Millar, R.P., Jabbour, H.N. Endocrinology (2008) [Pubmed]
  16. EG-VEGF and Bv8: a novel family of tissue-restricted angiogenic factors. Ferrara, N., LeCouter, J., Lin, R., Peale, F. Biochim. Biophys. Acta (2004) [Pubmed]
  17. Correlation of four vascular specific growth factors with carcinogenesis and portal vein tumor thrombus formation in human hepatocellular carcinoma. Li, Q., Xu, B., Fu, L., Hao, X.S. J. Exp. Clin. Cancer Res. (2006) [Pubmed]
  18. Prokineticins (endocrine gland-derived vascular endothelial growth factor and BV8) in the bovine ovary: expression and role as mitogens and survival factors for corpus luteum-derived endothelial cells. Kisliouk, T., Podlovni, H., Spanel-Borowski, K., Ovadia, O., Zhou, Q.Y., Meidan, R. Endocrinology (2005) [Pubmed]
  19. Molecular cloning and characterization of prokineticin receptors. Soga, T., Matsumoto, S., Oda, T., Saito, T., Hiyama, H., Takasaki, J., Kamohara, M., Ohishi, T., Matsushime, H., Furuichi, K. Biochim. Biophys. Acta (2002) [Pubmed]
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