title: Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitro by ghrelin.
abstract: BACKGROUND
  Ghrelin is a 28 amino acid peptide hormone that is expressed in the stomach and a range of peripheral tissues, where it frequently acts as an autocrine/paracrine growth factor. Ghrelin is modified by a unique acylation required for it to activate its cognate receptor, the growth hormone secretagogue receptor (GHSR), which mediates many of the actions of ghrelin. Recently, the enzyme responsible for adding the fatty acid residue (octanoyl/acyl group) to the third amino acid of ghrelin, GOAT (ghrelin O-acyltransferase), was identified.
  
  
  METHODS
  We used cell culture, quantitative real-time reverse transcription (RT)-PCR and immunohistochemistry to demonstrate the expression of GOAT in prostate cancer cell lines and tissues from patients. Real-time RT-PCR was used to demonstrate the expression of prohormone convertase (PC)1/3, PC2 and furin in prostate cancer cell lines. Prostate-derived cell lines were treated with ghrelin and desacyl ghrelin and the effect on GOAT expression was measured using quantitative RT-PCR.
  
  
  RESULTS
  We have demonstrated that GOAT mRNA and protein are expressed in the normal prostate and human prostate cancer tissue samples. The RWPE-1 and RWPE-2 normal prostate-derived cell lines and the LNCaP, DU145, and PC3 prostate cancer cell lines express GOAT and at least one other enzyme that is necessary to produce mature, acylated ghrelin from proghrelin (PC1/3, PC2 or furin). Finally, ghrelin, but not desacyl ghrelin (unacylated ghrelin), can directly regulate the expression of GOAT in the RWPE-1 normal prostate derived cell line and the PC3 prostate cancer cell line. Ghrelin treatment (100nM) for 6 hours significantly decreased GOAT mRNA expression two-fold (P < 0.05) in the PC3 prostate cancer cell line, however, ghrelin did not regulate GOAT expression in the DU145 and LNCaP prostate cancer cell lines.
  
  
  CONCLUSIONS
  This study demonstrates that GOAT is expressed in prostate cancer specimens and cell lines. Ghrelin regulates GOAT expression, however, this is likely to be cell-type specific. The expression of GOAT in prostate cancer supports the hypothesis that the ghrelin axis has autocrine/paracrine roles. We propose that the RWPE-1 prostate cell line and the PC3 prostate cancer cell line may be useful for investigating GOAT regulation and function.
authors.affiliation: Ghrelin Research Group, Translational Research Institute - Institute of Health and Biomedical Innovation, Queensland University of Technology, 37 Kent St, Woolloongabba, Queensland, 4102, Australia.
authors.forename: Inge
authors.initials: I
authors.lastname: Seim
authors.forename: Penny L
authors.initials: PL
authors.lastname: Jeffery
authors.forename: Laura
authors.initials: L
authors.lastname: de Amorim
authors.forename: Carina M
authors.initials: CM
authors.lastname: Walpole
authors.forename: Jenny
authors.initials: J
authors.lastname: Fung
authors.forename: Eliza J
authors.initials: EJ
authors.lastname: Whiteside
authors.forename: Rohan
authors.initials: R
authors.lastname: Lourie
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Herington
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Chopin
mesh_terms: D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D045683:Furin / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D054439:Ghrelin / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D045664:Proprotein Convertase 1 / Q000235:genetics / Q000378:metabolism; D045706:Proprotein Convertase 2 / Q000235:genetics / Q000378:metabolism; D011467:Prostate / Q000201:enzymology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054439:Ghrelin; D000217:Acyltransferases; C542776:MBOAT4 protein, human; D045683:Furin; D045664:Proprotein Convertase 1; D045706:Proprotein Convertase 2