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

Seim, Inge, Lubik, Amy A., Lehman, Melanie, Tomlinson, Nadine, Whiteside, Eliza, Herington, Adrian C., Nelson, Colleen C., & Chopin, Lisa K. (2012) Cloning of a novel insulin-regulated ghrelin transcript in prostate cancer. Journal of Molecular Endocrinology.

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Ghrelin is a multifunctional hormone, with roles in stimulating appetite and regulating energy balance, insulin secretion and glucose homeostasis. 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 AA preproghrelin isoform that codes for the 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 has 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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ID Code: 56346
Item Type: Journal Article
Refereed: Yes
Keywords: ghrelin, cryptic exon, splicing, testis, prostate cancer, insulin
DOI: 10.1530/JME-12-0150
ISSN: 0952-5041 (online) 1479-6813 (print)
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Genetics (111203)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 Society for Endocrinology, United Kingdom.
Copyright Statement: If ............ you prefer not to choose the Open Access Option, you may still publish in Society for Endocrinology journals, without paying any publication charges, but the full text of your paper will be subject to access controls for an initial period, currently one year. (During this period it will only be accessible by subscribers or other readers who select ‘pay per view’.) In addition, you will not be able to release your article on open repositories (such as PubMed Central, institutional repositories or other web sites) until a year after final publication, and then only as the accepted manuscript, not the final published version of record. For details, see the Society's policy on self-archiving.
Deposited On: 10 Jan 2013 22:17
Last Modified: 01 Apr 2014 22:42

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