Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitro by ghrelin

Seim, Inge and Jeffery, Penny L. and de Amorim, Laura and Walpole, Carina M. and Fung, Jenny and Whiteside, Eliza J. and Lourie, Rohan and Herington, Adrian C. and Chopin, Lisa K. (2013) Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitro by ghrelin. Reproductive Biology and Endocrinology, 11 (1). pp. 70-78.

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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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: © 2013 Seim et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Faculty / Department / School: Historic - Faculty of Health, Engineering and Sciences - School of Health, Nursing and Midwifery
Date Deposited: 04 Nov 2014 23:21
Last Modified: 08 Mar 2017 02:01
Uncontrolled Keywords: acyl-modification; ghrelin; GOAT; prohormone convertase; prostate cancer
Fields of Research : 11 Medical and Health Sciences > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology
06 Biological Sciences > 0601 Biochemistry and Cell Biology > 060107 Enzymes
11 Medical and Health Sciences > 1101 Medical Biochemistry and Metabolomics > 110101 Medical Biochemistry: Amino Acids and Metabolites
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970106 Expanding Knowledge in the Biological Sciences
Identification Number or DOI: 10.1186/1477-7827-11-70
URI: http://eprints.usq.edu.au/id/eprint/26316

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