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

Article


Seim, Inge, Lubik, Amy A., Lehman, Melanie L., Tomlinson, Nadine, Whiteside, Eliza J., Herington, Adrian C., 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. https://doi.org/10.1530/JME-12-0150
Article Title

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

ERA Journal ID16429
Article CategoryArticle
AuthorsSeim, Inge (Author), Lubik, Amy A. (Author), Lehman, Melanie L. (Author), Tomlinson, Nadine (Author), Whiteside, Eliza J. (Author), Herington, Adrian C. (Author), Nelson, Colleen C. (Author) and Chopin, Lisa K. (Author)
Journal TitleJournal of Molecular Endocrinology
Journal Citation50 (2), pp. 179-191
Number of Pages13
Year2013
Place of PublicationBristol, United Kingdom
ISSN0952-5041
1479-6813
Digital Object Identifier (DOI)https://doi.org/10.1530/JME-12-0150
Web Address (URL)http://jme.endocrinology-journals.org/content/50/2/179
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.

Keywordscancer; cryptic exon; ghrelin; insulin; prostate; splicing; testis
ANZSRC Field of Research 2020321101. Cancer cell biology
320501. Medical biochemistry - amino acids and metabolites
310505. Gene expression (incl. microarray and other genome-wide approaches)
Public Notes

© 2013 Society for Endocrinology. Permanent restricted access to published version due to publisher copyright policy.

Byline AffiliationsQueensland University of Technology
Vancouver Prostate Centre, Canada
Institution of OriginUniversity of Southern Queensland
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