IGF2 increases de novo steroidogenesis in prostate cancer cells

Lubik, Amy, Gunter, Jennifer, Hollier, Brett G., Fazli, Ladan, Ettinger, Susan, Stylianou, Nataly, Adomat, Hans , Hendy, Stephen C., Gleave, Martin, Pollak, Michael N., Herington, Adrian, & Nelson, Colleen C. (2013) IGF2 increases de novo steroidogenesis in prostate cancer cells. Endocrine Related Cancer, 20(2), pp. 173-186.

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Abstract

Androgen-dependent pathways regulate maintenance and growth of normal and malignant prostate tissues. Androgen deprivation therapy (ADT) exploits this dependence and is used to treat metastatic prostate cancer; however, regression initially seen with ADT gives way to development of incurable castration-resistant prostate cancer (CRPC). Although ADT generates a therapeutic response, it is also associated with a pattern of metabolic alterations consistent with metabolic syndrome including elevated circulating insulin. Because CRPC cells are capable of synthesizing androgens de novo, we hypothesized that insulin may also influence steroidogenesis in CRPC. In this study, we examined this hypothesis by evaluating the effect of insulin on steroid synthesis in prostate cancer cell lines. Treatment with 10 nmol/L insulin increased mRNA and protein expression of steroidogenesis enzymes and upregulated the insulin receptor substrate insulin receptor substrate 2 (IRS-2). Similarly, insulin treatment upregulated intracellular testosterone levels and secreted androgens, with the concentrations of steroids observed similar to the levels reported in prostate cancer patients. With similar potency to dihydrotestosterone, insulin treatment resulted in increased mRNA expression of prostate-specific antigen. CRPC progression also correlated with increased expression of IRS-2 and insulin receptor in vivo. Taken together, our findings support the hypothesis that the elevated insulin levels associated with therapeutic castration may exacerbate progression of prostate cancer to incurable CRPC in part by enhancing steroidogenesis.

Impact and interest:

20 citations in Scopus
15 citations in Web of Science®
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ID Code: 56345
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Additional URLs:
Keywords: insulin, prostate cancer, steroidogenesis, androgen-dependent pathways, androgen deprivation therapy
DOI: 10.1530/ERC-12-0250
ISSN: 1479-6821(online) 1351-0088 (print)
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL BIOCHEMISTRY AND METABOLOMICS (110100) > Medical Biochemistry and Metabolomics not elsewhere classified (110199)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 10 Jan 2013 20:55
Last Modified: 17 Jul 2017 12:01

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