Cloning of a novel insulin-regulated ghrelin transcript in prostate cancer

Seim, Inge and Lubik, Amy A. and Lehman, Melanie L. and Tomlinson, Nadine and Whiteside, Eliza J. and Herington, Adrian C. and Nelson, Colleen C. and Chopin, Lisa K. (2013) Cloning of a novel insulin-regulated ghrelin transcript in prostate cancer. Journal of Molecular Endocrinology, 50 (2). pp. 179-191. ISSN 0952-5041

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Abstract

Ghrelin is a multifunctional hormone, with roles in stimulating appetite and regulating energy balance, insulin secretion and glucose homoeostasis. The ghrelin gene locus (GHRL) is highly complex and gives rise to a range of novel transcripts derived from alternative first exons and internally spliced exons. The wild-type transcript encodes a 117 amino acid preprohormone that is processed to yield the 28 amino acid peptide ghrelin. Here, we identified insulin-responsive transcription corresponding to cryptic exons in intron 2 of the human ghrelin gene. A transcript, termed in2c-ghrelin (intron 2-cryptic), was cloned from the testis and the LNCaP prostate cancer cell line. This transcript may encode an 83 amino acid preproghrelin isoform that codes for ghrelin, but not obestatin. It is expressed in a limited number of normal tissues and in tumours of the prostate, testis, breast and ovary. Finally, we confirmed that in2c-ghrelin transcript expression, as well as the recently described in1-ghrelin transcript, is significantly upregulated by insulin in cultured prostate cancer cells. Metabolic syndrome and hyperinsulinaemia have been associated with prostate cancer risk and progression. This may be particularly significant after androgen deprivation therapy for prostate cancer, which induces hyperinsulinaemia, and this could contribute to castrate-resistant prostate cancer growth. We have previously demonstrated that ghrelin stimulates prostate cancer cell line proliferation in vitro. This study is the first description of insulin regulation of a ghrelin transcript in cancer and should provide further impetus for studies into the expression, regulation and function of ghrelin gene products.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: © 2013 Society for Endocrinology. Permanent restricted access to published version due to publisher copyright policy.
Faculty / Department / School: Historic - Faculty of Sciences - Department of Biological and Physical Sciences
Date Deposited: 05 Nov 2014 23:03
Last Modified: 24 Jan 2017 00:59
Uncontrolled Keywords: cancer; cryptic exon; ghrelin; insulin; prostate; splicing; testis
Fields of Research : 11 Medical and Health Sciences > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology
11 Medical and Health Sciences > 1101 Medical Biochemistry and Metabolomics > 110101 Medical Biochemistry: Amino Acids and Metabolites
06 Biological Sciences > 0604 Genetics > 060405 Gene Expression (incl. Microarray and other genome-wide approaches)
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970106 Expanding Knowledge in the Biological Sciences
Identification Number or DOI: 10.1530/JME-12-0150
URI: http://eprints.usq.edu.au/id/eprint/26318

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